rs6670678

Variant names:

• chr1-169568440-A-G
• rs6670678
• NM_000130.5:c.373+3781T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-169568440-A-G
• chr1-169568440-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000130.5(F5):​c.373+3781T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 151,966 control chromosomes in the GnomAD database, including 35,623 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (35623 hom., cov: 33)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.846
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.373+3781T>C		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.373+3781T>C		intron_variant	Intron 3 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.373+3781T>C		intron_variant	Intron 3 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102151 AN: 151848 Hom.: 35569 Cov.: 33

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.663

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.673 AC: 102267 AN: 151966 Hom.: 35623 Cov.: 33 AF XY: 0.677 AC XY: 50282 AN XY: 74286

African (AFR) AF: 0.840 AC: 34857 AN: 41516

American (AMR) AF: 0.704 AC: 10721 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2039 AN: 3472

East Asian (EAS) AF: 0.880 AC: 4534 AN: 5154

South Asian (SAS) AF: 0.589 AC: 2839 AN: 4818

European-Finnish (FIN) AF: 0.661 AC: 6981 AN: 10560

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.566 AC: 38405 AN: 67894

Other (OTH) AF: 0.663 AC: 1401 AN: 2112

Alfa AF: 0.622 Hom.: 7430

Bravo AF: 0.688

Asia WGS AF: 0.772 AC: 2678 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.46
PhyloP100		-0.85
Mutation Taster		=100/0	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: rs6670678; hg19: chr1-169537678;