rs7545236

Variant names:

• chr1-169560832-A-C
• rs7545236
• NM_000130.5:c.374-66T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-169560832-A-C
• chr1-169560832-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000130.5(F5):​c.374-66T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,416,802 control chromosomes in the GnomAD database, including 42,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (10859 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31786 hom.)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.31
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-169560832-A-C is Benign according to our data. Variant chr1-169560832-A-C is described in ClinVar as Benign. ClinVar VariationId is 1286244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.374-66T>G		intron_variant	Intron 3 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.374-66T>G		intron_variant	Intron 3 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.374-66T>G		intron_variant	Intron 3 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49561 AN: 151802 Hom.: 10837 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.294

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

GnomAD4 exome AF: 0.197 AC: 248991 AN: 1264882 Hom.: 31786 AF XY: 0.195 AC XY: 124318 AN XY: 638590

African (AFR) AF: 0.597 AC: 16978 AN: 28462

American (AMR) AF: 0.274 AC: 11970 AN: 43708

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 5140 AN: 24772

East Asian (EAS) AF: 0.596 AC: 22886 AN: 38398

South Asian (SAS) AF: 0.172 AC: 14097 AN: 81782

European-Finnish (FIN) AF: 0.256 AC: 13485 AN: 52610

Middle Eastern (MID) AF: 0.214 AC: 799 AN: 3726

European-Non Finnish (NFE) AF: 0.161 AC: 150822 AN: 937930

Other (OTH) AF: 0.240 AC: 12814 AN: 53494

GnomAD4 genome AF: 0.327 AC: 49632 AN: 151920 Hom.: 10859 Cov.: 32 AF XY: 0.328 AC XY: 24397 AN XY: 74280

African (AFR) AF: 0.597 AC: 24696 AN: 41398

American (AMR) AF: 0.293 AC: 4478 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3470

East Asian (EAS) AF: 0.652 AC: 3331 AN: 5112

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

European-Finnish (FIN) AF: 0.256 AC: 2706 AN: 10584

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

European-Non Finnish (NFE) AF: 0.177 AC: 12001 AN: 67956

Other (OTH) AF: 0.307 AC: 648 AN: 2114

Alfa AF: 0.207 Hom.: 2913

Bravo AF: 0.345

Asia WGS AF: 0.451 AC: 1568 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.63
PhyloP100		1.3
Mutation Taster		=99/1	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: rs7545236; hg19: chr1-169530070;