rs12131397

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-169524715-A-C
• chr1-169524715-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.431
• Publications: 12 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: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
F5	NM_000130.5	c.5788+122T>G		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>G		intron_variant	Intron 19 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.5803+122T>G		intron_variant	Intron 19 of 24	5		ENSP00000356770.3

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

African (AFR) AF: 0.293 AC: 5291 AN: 18074

American (AMR) AF: 0.240 AC: 9200 AN: 38336

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 9428 AN: 20534

East Asian (EAS) AF: 0.0311 AC: 1047 AN: 33650

South Asian (SAS) AF: 0.291 AC: 19601 AN: 67318

European-Finnish (FIN) AF: 0.530 AC: 25409 AN: 47926

Middle Eastern (MID) AF: 0.406 AC: 1730 AN: 4262

European-Non Finnish (NFE) AF: 0.536 AC: 229379 AN: 428266

Other (OTH) AF: 0.443 AC: 15337 AN: 34652

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

African (AFR) AF: 0.285 AC: 11823 AN: 41430

American (AMR) AF: 0.312 AC: 4756 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1539 AN: 3468

East Asian (EAS) AF: 0.0409 AC: 212 AN: 5182

South Asian (SAS) AF: 0.276 AC: 1331 AN: 4818

European-Finnish (FIN) AF: 0.526 AC: 5554 AN: 10558

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35774 AN: 67926

Other (OTH) AF: 0.401 AC: 846 AN: 2112

Alfa AF: 0.479 Hom.: 32525

Bravo AF: 0.391

Asia WGS AF: 0.151 AC: 526 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.78
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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;