chr1-169550860-A-G

Variant names:

• chr1-169550860-A-G
• rs10800456
• NM_000130.5:c.1297-121T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000130.5(F5):​c.1297-121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 725,332 control chromosomes in the GnomAD database, including 71,226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (16103 hom., cov: 31)
  • Exomes 𝑓: 0.41 (55123 hom.)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.467
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-169550860-A-G is Benign according to our data. Variant chr1-169550860-A-G is described in ClinVar as Benign. ClinVar VariationId is 1268340.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	NM_000130.5	MANE Select	c.1297-121T>C		intron	N/A	NP_000121.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	ENST00000367797.9	TSL:1 MANE Select	c.1297-121T>C		intron	N/A	ENSP00000356771.3
	F5	ENST00000367796.3	TSL:5	c.1297-121T>C		intron	N/A	ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66531 AN: 151938 Hom.: 16059 Cov.: 31

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.407 AC: 233162 AN: 573276 Hom.: 55123 AF XY: 0.408 AC XY: 125897 AN XY: 308200

African (AFR) AF: 0.537 AC: 8389 AN: 15630

American (AMR) AF: 0.609 AC: 20393 AN: 33508

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 4616 AN: 18814

East Asian (EAS) AF: 0.908 AC: 28795 AN: 31730

South Asian (SAS) AF: 0.523 AC: 31674 AN: 60554

European-Finnish (FIN) AF: 0.424 AC: 15930 AN: 37552

Middle Eastern (MID) AF: 0.343 AC: 1072 AN: 3128

European-Non Finnish (NFE) AF: 0.322 AC: 109979 AN: 341824

Other (OTH) AF: 0.403 AC: 12314 AN: 30536

GnomAD4 genome AF: 0.438 AC: 66628 AN: 152056 Hom.: 16103 Cov.: 31 AF XY: 0.452 AC XY: 33629 AN XY: 74360

African (AFR) AF: 0.548 AC: 22700 AN: 41460

American (AMR) AF: 0.531 AC: 8123 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 890 AN: 3470

East Asian (EAS) AF: 0.895 AC: 4626 AN: 5168

South Asian (SAS) AF: 0.552 AC: 2666 AN: 4826

European-Finnish (FIN) AF: 0.432 AC: 4572 AN: 10586

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21862 AN: 67950

Other (OTH) AF: 0.434 AC: 914 AN: 2108

Alfa AF: 0.348 Hom.: 17738

Bravo AF: 0.450

Asia WGS AF: 0.720 AC: 2499 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.73
PhyloP100		-0.47
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: rs10800456; hg19: chr1-169520098; COSMIC: COSV63122199;