rs2239854

Positions:

• chr1-169556570-G-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.952+76C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,430,544 control chromosomes in the GnomAD database, including 69,629 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6359 hom., cov: 31)
  • Exomes 𝑓: 0.31 (63270 hom.)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.900

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=-0.91).
• BP6: Variant 1-169556570-G-A is Benign according to our data. Variant chr1-169556570-G-A is described in ClinVar as [Benign]. Clinvar id is 1247250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F5	NM_000130.5	c.952+76C>T		intron_variant		ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.952+76C>T		intron_variant		1	NM_000130.5	ENSP00000356771	P2
F5	ENST00000367796.3	c.952+76C>T		intron_variant		5		ENSP00000356770	A2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42918 AN: 151864 Hom.: 6341 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.311 AC: 397370 AN: 1278562 Hom.: 63270 AF XY: 0.311 AC XY: 199732 AN XY: 642026

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.436

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.349

Gnomad4 FIN exome AF: 0.358

Gnomad4 NFE exome AF: 0.307

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.283 AC: 42971 AN: 151982 Hom.: 6359 Cov.: 31 AF XY: 0.288 AC XY: 21369 AN XY: 74272

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.287

Alfa AF: 0.299 Hom.: 3072

Bravo AF: 0.280

Asia WGS AF: 0.283 AC: 984 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.1
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2239854; hg19: chr1-169525808; COSMIC: COSV63124099;