chr1-169531243-G-A

Variant names:

• chr1-169531243-G-A
• rs9332618
• NM_000130.5:c.4972-221C>T

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.4972-221C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0885 in 151,934 control chromosomes in the GnomAD database, including 782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.088 (782 hom., cov: 33)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.143
• Publications: 15 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=-0.84).
• BP6: Variant 1-169531243-G-A is Benign according to our data. Variant chr1-169531243-G-A is described in ClinVar as [Benign]. Clinvar id is 1287709.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.4972-221C>T		intron_variant	Intron 14 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.4972-221C>T		intron_variant	Intron 14 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.4987-221C>T		intron_variant	Intron 14 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.0885 AC: 13433 AN: 151816 Hom.: 781 Cov.: 33

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0861

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

GnomAD4 genome AF: 0.0885 AC: 13439 AN: 151934 Hom.: 782 Cov.: 33 AF XY: 0.0898 AC XY: 6670 AN XY: 74252

African (AFR) AF: 0.0429 AC: 1772 AN: 41282

American (AMR) AF: 0.0623 AC: 952 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0979 AC: 340 AN: 3472

East Asian (EAS) AF: 0.0382 AC: 198 AN: 5188

South Asian (SAS) AF: 0.103 AC: 496 AN: 4822

European-Finnish (FIN) AF: 0.164 AC: 1735 AN: 10580

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7646 AN: 68002

Other (OTH) AF: 0.0848 AC: 179 AN: 2112

Alfa AF: 0.104 Hom.: 857

Bravo AF: 0.0792

Asia WGS AF: 0.0630 AC: 219 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 11, 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	-0.84
CADD	Benign	4.0
DANN	Benign	0.57
PhyloP100		0.14
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: rs9332618; hg19: chr1-169500481;