1-169543286-C-T

Variant names:

• chr1-169543286-C-T
• rs2239852
• NM_000130.5:c.1976-172G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000130.5(F5):​c.1976-172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,896 control chromosomes in the GnomAD database, including 12,903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.40 (12903 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.854

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-169543286-C-T is Benign according to our data. Variant chr1-169543286-C-T is described in ClinVar as [Benign]. Clinvar id is 1254957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.1976-172G>A		intron_variant	Intron 12 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.1976-172G>A		intron_variant	Intron 12 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.1991-172G>A		intron_variant	Intron 12 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59996 AN: 151778 Hom.: 12871 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.396 AC: 60079 AN: 151896 Hom.: 12903 Cov.: 32 AF XY: 0.407 AC XY: 30199 AN XY: 74216

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.897

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.416

Alfa AF: 0.362 Hom.: 10057

Bravo AF: 0.407

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.26
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs2239852; hg19: chr1-169512524;