rs6022

Variant names:

• chr1-169560588-C-A
• rs6022
• NM_000130.5:c.552G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-169560588-C-A
• chr1-169560588-C-G
• chr1-169560588-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_000130.5(F5):​c.552G>T​(p.Ser184Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,613,178 control chromosomes in the GnomAD database, including 47,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S184S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.32 (10496 hom., cov: 31)
  • Exomes 𝑓: 0.20 (37433 hom.)
• Consequence: F5 NM_000130.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.639
• Publications: 29 publications found

Genes affected

F5 (HGNC:3542): (coagulation factor V) This gene encodes an essential cofactor of the blood coagulation cascade. This factor circulates in plasma, and is converted to the active form by the release of the activation peptide by thrombin during coagulation. This generates a heavy chain and a light chain which are held together by calcium ions. The activated protein is a cofactor that participates with activated coagulation factor X to activate prothrombin to thrombin. Defects in this gene result in either an autosomal recessive hemorrhagic diathesis or an autosomal dominant form of thrombophilia, which is known as activated protein C resistance. [provided by RefSeq, Oct 2008]

F5 Gene-Disease associations (from GenCC):

• thrombophilia due to activated protein C resistance

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• congenital factor V deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• East Texas bleeding disorder

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 1-169560588-C-A is Benign according to our data. Variant chr1-169560588-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 255212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.639 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.552G>T	p.Ser184Ser	synonymous_variant	Exon 4 of 25	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.552G>T	p.Ser184Ser	synonymous_variant	Exon 4 of 25	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.552G>T	p.Ser184Ser	synonymous_variant	Exon 4 of 25	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48902 AN: 151662 Hom.: 10474 Cov.: 31

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.300

GnomAD2 exomes AF: 0.261 AC: 65679 AN: 251384 AF XY: 0.248

Gnomad AFR exome AF: 0.589

Gnomad AMR exome AF: 0.269

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.678

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.237

GnomAD4 exome AF: 0.202 AC: 294949 AN: 1461400 Hom.: 37433 Cov.: 35 AF XY: 0.199 AC XY: 144917 AN XY: 727034

African (AFR) AF: 0.594 AC: 19863 AN: 33438

American (AMR) AF: 0.273 AC: 12218 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 5484 AN: 26120

East Asian (EAS) AF: 0.600 AC: 23826 AN: 39698

South Asian (SAS) AF: 0.175 AC: 15055 AN: 86256

European-Finnish (FIN) AF: 0.257 AC: 13722 AN: 53418

Middle Eastern (MID) AF: 0.215 AC: 1238 AN: 5768

European-Non Finnish (NFE) AF: 0.170 AC: 188674 AN: 1111644

Other (OTH) AF: 0.246 AC: 14869 AN: 60364

GnomAD4 genome AF: 0.323 AC: 48970 AN: 151778 Hom.: 10496 Cov.: 31 AF XY: 0.325 AC XY: 24076 AN XY: 74184

African (AFR) AF: 0.582 AC: 24080 AN: 41362

American (AMR) AF: 0.292 AC: 4447 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 710 AN: 3462

East Asian (EAS) AF: 0.652 AC: 3338 AN: 5118

South Asian (SAS) AF: 0.193 AC: 932 AN: 4818

European-Finnish (FIN) AF: 0.256 AC: 2696 AN: 10542

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 11994 AN: 67914

Other (OTH) AF: 0.305 AC: 644 AN: 2110

Alfa AF: 0.209 Hom.: 8249

Bravo AF: 0.340

Asia WGS AF: 0.450 AC: 1563 AN: 3478

EpiCase AF: 0.173

EpiControl AF: 0.175

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Thrombophilia due to activated protein C resistance Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital factor V deficiency Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Budd-Chiari syndrome Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Factor V deficiency Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Thrombophilia due to thrombin defect Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.096
DANN	Benign	0.40
PhyloP100		-0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=79/21	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6022; hg19: chr1-169529826; COSMIC: COSV63123820;