dbSNP rs693335: F10:c.231+517G>A (chr13-113130129-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS1

The NM_000504.4(F10):c.231+517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 193,492 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00021 ( 0 hom., cov: 35)

Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

F10
NM_000504.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.59

Publications

3 publications found

Variant links:

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 links:

F10-AS1 (HGNC:40225): (F10 antisense RNA 1)

F10-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000386 (17/44006) while in subpopulation NFE AF = 0.000603 (16/26534). AF 95% confidence interval is 0.000378. There are 0 homozygotes in GnomAdExome4. There are 10 alleles in the male GnomAdExome4 subpopulation. Median coverage is 0. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
F10	NM_000504.4 link	c.231+517G>A	intron_variant	Intron 2 of 7	ENST00000375559.8	NP_000495.1
F10	NM_001312674.2 link	c.231+517G>A	intron_variant	Intron 2 of 6		NP_001299603.1
F10	NM_001312675.2 link	c.231+517G>A	intron_variant	Intron 2 of 7		NP_001299604.1
F10-AS1	NR_126424.1 link	n.-83C>T	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F10	ENST00000375559.8 link	c.231+517G>A		intron_variant	Intron 2 of 7	1	NM_000504.4	ENSP00000364709.3

Frequencies

GnomAD3 genomes

AF:

0.000207

AC:

AN:

149486

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000383

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000386

AC:

AN:

44006

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

22588

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

762

American (AMR)

AF:

0.00

AC:

AN:

3452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

814

East Asian (EAS)

AF:

0.00

AC:

AN:

2648

South Asian (SAS)

AF:

0.00

AC:

AN:

5554

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1736

Middle Eastern (MID)

AF:

0.00

AC:

AN:

168

European-Non Finnish (NFE)

AF:

0.000603

AC:

AN:

26534

Other (OTH)

AF:

0.000428

AC:

AN:

2338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000207

AC:

AN:

149486

Hom.:

Cov.:

AF XY:

0.000178

AC XY:

AN XY:

73070

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39078

American (AMR)

AF:

0.00

AC:

AN:

15156

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000472

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.000383

AC:

AN:

67918

Other (OTH)

AF:

0.00

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00109

Hom.:

1257

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.89

(source)

DANN

Benign

0.97

PhyloP100

-2.6

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over