rs7545236

Positions:

• chr1-169560832-A-C
• chr1-169560832-A-G

Variant summary

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

The ENST00000367797.9(F5):​c.374-66T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,416,802 control chromosomes in the GnomAD database, including 42,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (10859 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31786 hom.)
• Consequence: F5 ENST00000367797.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.31

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=-0.83).
• BP6: Variant 1-169560832-A-C is Benign according to our data. Variant chr1-169560832-A-C is described in ClinVar as [Benign]. Clinvar id is 1286244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F5	NM_000130.5	c.374-66T>G		intron_variant		ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.374-66T>G		intron_variant		1	NM_000130.5	ENSP00000356771	P2
F5	ENST00000367796.3	c.374-66T>G		intron_variant		5		ENSP00000356770	A2

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49561 AN: 151802 Hom.: 10837 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.197 AC: 248991 AN: 1264882 Hom.: 31786 AF XY: 0.195 AC XY: 124318 AN XY: 638590

Gnomad4 AFR exome AF: 0.597

Gnomad4 AMR exome AF: 0.274

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.596

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.256

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.327 AC: 49632 AN: 151920 Hom.: 10859 Cov.: 32 AF XY: 0.328 AC XY: 24397 AN XY: 74280

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.193

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.307

Alfa AF: 0.206 Hom.: 2245

Bravo AF: 0.345

Asia WGS AF: 0.451 AC: 1568 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	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.1
DANN	Benign	0.63

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: rs7545236; hg19: chr1-169530070;