chr1-169551126-C-T

Variant names:

• chr1-169551126-C-T
• rs10158595
• NM_000130.5:c.1297-387G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000130.5(F5):​c.1297-387G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 151,976 control chromosomes in the GnomAD database, including 4,337 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4337 hom., cov: 31)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.1297-387G>A		intron_variant	Intron 8 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.1297-387G>A		intron_variant	Intron 8 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.1297-387G>A		intron_variant	Intron 8 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35856 AN: 151858 Hom.: 4323 Cov.: 31

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.236 AC: 35901 AN: 151976 Hom.: 4337 Cov.: 31 AF XY: 0.241 AC XY: 17886 AN XY: 74268

Gnomad4 AFR AF: 0.204

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.239

Alfa AF: 0.224 Hom.: 4416

Bravo AF: 0.240

Asia WGS AF: 0.276 AC: 957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.33
DANN	Benign	0.38

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: rs10158595; hg19: chr1-169520364;