1-169524715-A-T

Variant names:

• chr1-169524715-A-T
• rs12131397
• NM_000130.5:c.5788+122T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000130.5(F5):​c.5788+122T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000576 in 694,128 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431
• Publications: 0 publications found

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]

F5 Gene-Disease associations (from GenCC):

• thrombophilia due to activated protein C resistance

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• congenital factor V deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• East Texas bleeding disorder

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.5788+122T>A		intron_variant	Intron 19 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.5788+122T>A		intron_variant	Intron 19 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.5803+122T>A		intron_variant	Intron 19 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000576 AC: 4 AN: 694128 Hom.: 0 AF XY: 0.00000270 AC XY: 1 AN XY: 370582

African (AFR) AF: 0.00 AC: 0 AN: 18102

American (AMR) AF: 0.00 AC: 0 AN: 38364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20560

East Asian (EAS) AF: 0.00 AC: 0 AN: 33654

South Asian (SAS) AF: 0.00 AC: 0 AN: 67348

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4262

European-Non Finnish (NFE) AF: 0.00000932 AC: 4 AN: 429134

Other (OTH) AF: 0.00 AC: 0 AN: 34694

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.78
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs12131397; hg19: chr1-169493953;