rs3211727

Variant names:

• chr13-113126704-G-A
• rs3211727
• NM_000504.4:c.71-2748G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-113126704-G-A
• chr13-113126704-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000504.4(F10):​c.71-2748G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,164 control chromosomes in the GnomAD database, including 3,430 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 0.19 (3430 hom., cov: 32)
• Consequence: F10 NM_000504.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02
• Publications: 3 publications found

Genes affected

F10 (HGNC:3528): (coagulation factor X) This gene encodes the vitamin K-dependent coagulation factor X of the blood coagulation cascade. This factor undergoes multiple processing steps before its preproprotein is converted to a mature two-chain form by the excision of the tripeptide RKR. Two chains of the factor are held together by 1 or more disulfide bonds; the light chain contains 2 EGF-like domains, while the heavy chain contains the catalytic domain which is structurally homologous to those of the other hemostatic serine proteases. The mature factor is activated by the cleavage of the activation peptide by factor IXa (in the intrisic pathway), or by factor VIIa (in the extrinsic pathway). The activated factor then converts prothrombin to thrombin in the presence of factor Va, Ca+2, and phospholipid during blood clotting. Mutations of this gene result in factor X deficiency, a hemorrhagic condition of variable severity. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing to generate mature polypeptides. [provided by RefSeq, Aug 2015]

F10 Gene-Disease associations (from GenCC):

• congenital factor X deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F10	NM_000504.4	c.71-2748G>A		intron_variant	Intron 1 of 7	ENST00000375559.8	NP_000495.1
F10	NM_001312674.2	c.71-2748G>A		intron_variant	Intron 1 of 6		NP_001299603.1
F10	NM_001312675.2	c.71-2748G>A		intron_variant	Intron 1 of 7		NP_001299604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F10	ENST00000375559.8	c.71-2748G>A		intron_variant	Intron 1 of 7	1	NM_000504.4	ENSP00000364709.3

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28490 AN: 152046 Hom.: 3421 Cov.: 32

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.0995

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.187 AC: 28508 AN: 152164 Hom.: 3430 Cov.: 32 AF XY: 0.193 AC XY: 14378 AN XY: 74368

African (AFR) AF: 0.0493 AC: 2050 AN: 41556

American (AMR) AF: 0.272 AC: 4161 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0995 AC: 345 AN: 3468

East Asian (EAS) AF: 0.385 AC: 1992 AN: 5172

South Asian (SAS) AF: 0.153 AC: 735 AN: 4812

European-Finnish (FIN) AF: 0.332 AC: 3510 AN: 10572

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15013 AN: 67992

Other (OTH) AF: 0.194 AC: 410 AN: 2110

Alfa AF: 0.195 Hom.: 4560

Bravo AF: 0.184

Asia WGS AF: 0.277 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.62
PhyloP100		-3.0
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: rs3211727; hg19: chr13-113781018;