13-113123195-A-G

Variant summary

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

The NM_000504.4(F10):c.70+270A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,112 control chromosomes in the GnomAD database, including 3,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3657 hom., cov: 32)
• Consequence: F10 NM_000504.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.427

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 13-113123195-A-G is Benign according to our data. Variant chr13-113123195-A-G is described in ClinVar as [Benign]. Clinvar id is 1249655.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F10	NM_000504.4	c.70+270A>G		intron_variant		ENST00000375559.8
F10	NM_001312674.2	c.70+270A>G		intron_variant
F10	NM_001312675.2	c.70+270A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F10	ENST00000375559.8	c.70+270A>G		intron_variant		1	NM_000504.4	P1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32313 AN: 151994 Hom.: 3651 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.213 AC: 32348 AN: 152112 Hom.: 3657 Cov.: 32 AF XY: 0.210 AC XY: 15589 AN XY: 74376

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.198

Alfa AF: 0.232 Hom.: 4327

Bravo AF: 0.209

Asia WGS AF: 0.230 AC: 798 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	-0.88
Cadd	Benign	2.2
Dann	Benign	0.65

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: rs3211719; hg19: chr13-113777509;