rs6029

Variant names:

• chr1-169560735-C-T
• rs6029
• NM_000130.5:c.405G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-169560735-C-T
• chr1-169560735-C-G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000130.5(F5):​c.405G>A​(p.Ala135Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,612,154 control chromosomes in the GnomAD database, including 45,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (8966 hom., cov: 31)
  • Exomes 𝑓: 0.20 (36085 hom.)
• Consequence: F5 NM_000130.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -2.79
• Publications: 28 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: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae)
• 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 -16 ACMG points.

• BP6: Variant 1-169560735-C-T is Benign according to our data. Variant chr1-169560735-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000130.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	NM_000130.5	MANE Select	c.405G>A	p.Ala135Ala	synonymous	Exon 4 of 25	NP_000121.2	P12259

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	ENST00000367797.9	TSL:1 MANE Select	c.405G>A	p.Ala135Ala	synonymous	Exon 4 of 25	ENSP00000356771.3	P12259
	F5	ENST00000367796.3	TSL:5	c.405G>A	p.Ala135Ala	synonymous	Exon 4 of 25	ENSP00000356770.3	A0A0A0MRJ7
	F5	ENST00000904428.1		c.405G>A	p.Ala135Ala	synonymous	Exon 4 of 21	ENSP00000574487.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46101 AN: 151608 Hom.: 8956 Cov.: 31

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.285

GnomAD2 exomes AF: 0.257 AC: 64502 AN: 251236 AF XY: 0.245

Gnomad AFR exome AF: 0.525

Gnomad AMR exome AF: 0.267

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.679

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.200 AC: 292195 AN: 1460430 Hom.: 36085 Cov.: 35 AF XY: 0.198 AC XY: 143756 AN XY: 726508

African (AFR) AF: 0.530 AC: 17708 AN: 33412

American (AMR) AF: 0.271 AC: 12087 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 5479 AN: 26102

East Asian (EAS) AF: 0.600 AC: 23818 AN: 39694

South Asian (SAS) AF: 0.175 AC: 15048 AN: 86206

European-Finnish (FIN) AF: 0.257 AC: 13722 AN: 53420

Middle Eastern (MID) AF: 0.213 AC: 1094 AN: 5144

European-Non Finnish (NFE) AF: 0.170 AC: 188648 AN: 1111504

Other (OTH) AF: 0.242 AC: 14591 AN: 60270

GnomAD4 genome AF: 0.304 AC: 46142 AN: 151724 Hom.: 8966 Cov.: 31 AF XY: 0.306 AC XY: 22699 AN XY: 74120

African (AFR) AF: 0.518 AC: 21427 AN: 41376

American (AMR) AF: 0.284 AC: 4327 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3464

East Asian (EAS) AF: 0.651 AC: 3321 AN: 5102

South Asian (SAS) AF: 0.193 AC: 924 AN: 4788

European-Finnish (FIN) AF: 0.255 AC: 2692 AN: 10540

Middle Eastern (MID) AF: 0.169 AC: 49 AN: 290

European-Non Finnish (NFE) AF: 0.177 AC: 12004 AN: 67912

Other (OTH) AF: 0.288 AC: 607 AN: 2110

Alfa AF: 0.227 Hom.: 15000

Bravo AF: 0.319

Asia WGS AF: 0.447 AC: 1554 AN: 3478

EpiCase AF: 0.173

EpiControl AF: 0.175

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Thrombophilia due to activated protein C resistance (2)
-	-	1	Budd-Chiari syndrome (1)
-	-	1	Congenital factor V deficiency (1)
-	-	1	Factor V deficiency (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Thrombophilia due to thrombin defect (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Benign	0.51
PhyloP100		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.42		Position offset: -2

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

Other links and lift over

dbSNP: rs6029; hg19: chr1-169529973; COSMIC: COSV63124971;