1-169582297-T-C

Variant names:

• chr1-169582297-T-C
• rs9332684
• NM_000130.5:c.250+134A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000130.5(F5):​c.250+134A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 518,024 control chromosomes in the GnomAD database, including 147 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 0.020 (45 hom., cov: 32)
  • Exomes 𝑓: 0.019 (102 hom.)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 3 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: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0203 (2782/136858) while in subpopulation NFE AF = 0.0245 (1626/66334). AF 95% confidence interval is 0.0235. There are 45 homozygotes in GnomAd4. There are 1376 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 45 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000130.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	NM_000130.5	MANE Select	c.250+134A>G		intron	N/A	NP_000121.2	P12259

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F5	ENST00000367797.9	TSL:1 MANE Select	c.250+134A>G		intron	N/A	ENSP00000356771.3	P12259
	F5	ENST00000367796.3	TSL:5	c.250+134A>G		intron	N/A	ENSP00000356770.3	A0A0A0MRJ7
	F5	ENST00000904428.1		c.250+134A>G		intron	N/A	ENSP00000574487.1

Frequencies

GnomAD3 genomes AF: 0.0203 AC: 2780 AN: 136776 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.00565

Gnomad AMI AF: 0.0554

Gnomad AMR AF: 0.0236

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00432

Gnomad FIN AF: 0.0370

Gnomad MID AF: 0.0392

Gnomad NFE AF: 0.0245

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.0186 AC: 7071 AN: 381166 Hom.: 102 AF XY: 0.0175 AC XY: 3537 AN XY: 202220

African (AFR) AF: 0.00379 AC: 41 AN: 10830

American (AMR) AF: 0.0182 AC: 256 AN: 14088

Ashkenazi Jewish (ASJ) AF: 0.0377 AC: 419 AN: 11124

East Asian (EAS) AF: 0.0000755 AC: 2 AN: 26490

South Asian (SAS) AF: 0.00405 AC: 146 AN: 36084

European-Finnish (FIN) AF: 0.0342 AC: 1199 AN: 35084

Middle Eastern (MID) AF: 0.0238 AC: 38 AN: 1594

European-Non Finnish (NFE) AF: 0.0202 AC: 4535 AN: 224648

Other (OTH) AF: 0.0205 AC: 435 AN: 21224

GnomAD4 genome AF: 0.0203 AC: 2782 AN: 136858 Hom.: 45 Cov.: 32 AF XY: 0.0206 AC XY: 1376 AN XY: 66756

African (AFR) AF: 0.00563 AC: 176 AN: 31242

American (AMR) AF: 0.0235 AC: 330 AN: 14026

Ashkenazi Jewish (ASJ) AF: 0.0401 AC: 135 AN: 3368

East Asian (EAS) AF: 0.00 AC: 0 AN: 4248

South Asian (SAS) AF: 0.00476 AC: 22 AN: 4624

European-Finnish (FIN) AF: 0.0370 AC: 367 AN: 9928

Middle Eastern (MID) AF: 0.0390 AC: 11 AN: 282

European-Non Finnish (NFE) AF: 0.0245 AC: 1626 AN: 66334

Other (OTH) AF: 0.0341 AC: 65 AN: 1904

Alfa AF: 0.0227 Hom.: 22

Bravo AF: 0.0174

Asia WGS AF: 0.00404 AC: 14 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.47
DANN	Benign	0.35
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9332684; hg19: chr1-169551535;