chr1-169558618-T-C

Variant names:

• chr1-169558618-T-C
• rs3766117
• NM_000130.5:c.730+535A>G

Variant summary

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

The NM_000130.5(F5):​c.730+535A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,014 control chromosomes in the GnomAD database, including 13,524 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 0.35 (13524 hom., cov: 32)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.730+535A>G		intron_variant	Intron 5 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.730+535A>G		intron_variant	Intron 5 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.730+535A>G		intron_variant	Intron 5 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53814 AN: 151896 Hom.: 13485 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.355 AC: 53907 AN: 152014 Hom.: 13524 Cov.: 32 AF XY: 0.356 AC XY: 26464 AN XY: 74320

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.331

Alfa AF: 0.209 Hom.: 9728

Bravo AF: 0.377

Asia WGS AF: 0.458 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.74
DANN	Benign	0.59

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: rs3766117; hg19: chr1-169527856;