rs12131397

chr1-169524715-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000130.5(F5):c.5788+122T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 844,962 control chromosomes in the GnomAD database, including 93,824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (14376 hom., cov: 31)
  • Exomes 𝑓: 0.46 (79448 hom.)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.431

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-169524715-A-C is Benign according to our data. Variant chr1-169524715-A-C is described in ClinVar as [Benign]. Clinvar id is 1232273.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F5	NM_000130.5	c.5788+122T>G		intron_variant		ENST00000367797.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F5	ENST00000367797.9	c.5788+122T>G		intron_variant		1	NM_000130.5	P2
F5	ENST00000367796.3	c.5803+122T>G		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62537 AN: 151824 Hom.: 14376 Cov.: 31

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.0410

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.406

GnomAD4 exome AF: 0.457 AC: 316422 AN: 693018 Hom.: 79448 AF XY: 0.451 AC XY: 166890 AN XY: 370002

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.459

Gnomad4 EAS exome AF: 0.0311

Gnomad4 SAS exome AF: 0.291

Gnomad4 FIN exome AF: 0.530

Gnomad4 NFE exome AF: 0.536

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.412 AC: 62551 AN: 151944 Hom.: 14376 Cov.: 31 AF XY: 0.404 AC XY: 29975 AN XY: 74262

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.0409

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.401

Alfa AF: 0.486 Hom.: 24408

Bravo AF: 0.391

Asia WGS AF: 0.151 AC: 526 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.8
Dann	Benign	0.78

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: rs12131397; hg19: chr1-169493953;