rs2251102

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000504.4(F10):c.232-17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 1,178,712 control chromosomes in the GnomAD database, including 410,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 48841 hom., cov: 33)

Exomes 𝑓: 0.84 ( 361524 hom. )

Consequence

F10
NM_000504.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.31

Publications

8 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 Gene-Disease associations (from GenCC):

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

F10 links:

ENSG00000297191 (HGNC:):

ENSG00000297191 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000504.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 13-113138440-T-C is Benign according to our data. Variant chr13-113138440-T-C is described in ClinVar as Benign. ClinVar VariationId is 256307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000504.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
F10	NM_000504.4	MANE Select	c.232-17T>C	intron	N/A	NP_000495.1	Q5JVE7
F10	NM_001312674.2		c.232-17T>C	intron	N/A	NP_001299603.1
F10	NM_001312675.2		c.232-17T>C	intron	N/A	NP_001299604.1	Q5JVE8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
F10	ENST00000375559.8	TSL:1 MANE Select	c.232-17T>C	intron	N/A	ENSP00000364709.3	P00742
F10	ENST00000375551.7	TSL:1	c.232-17T>C	intron	N/A	ENSP00000364701.3	Q5JVE8
F10	ENST00000410083.6	TSL:1	n.232-17T>C	intron	N/A	ENSP00000386320.2	F8WBM7

Frequencies

GnomAD3 genomes

AF:

0.797

AC:

121197

AN:

152024

Hom.:

48802

Cov.:

show subpopulations

Gnomad AFR

AF:

0.664

Gnomad AMI

AF:

0.762

Gnomad AMR

AF:

0.864

Gnomad ASJ

AF:

0.844

Gnomad EAS

AF:

0.894

Gnomad SAS

AF:

0.835

Gnomad FIN

AF:

0.847

Gnomad MID

AF:

0.839

Gnomad NFE

AF:

0.843

Gnomad OTH

AF:

0.799

GnomAD2 exomes

AF:

0.842

AC:

202335

AN:

240164

AF XY:

0.844

show subpopulations

Gnomad AFR exome

AF:

0.655

Gnomad AMR exome

AF:

0.913

Gnomad ASJ exome

AF:

0.835

Gnomad EAS exome

AF:

0.888

Gnomad FIN exome

AF:

0.847

Gnomad NFE exome

AF:

0.841

Gnomad OTH exome

AF:

0.840

GnomAD4 exome

AF:

0.838

AC:

860113

AN:

1026570

Hom.:

361524

Cov.:

AF XY:

0.839

AC XY:

443520

AN XY:

528396

show subpopulations

African (AFR)

AF:

0.642

AC:

16036

AN:

24964

American (AMR)

AF:

0.908

AC:

37093

AN:

40844

Ashkenazi Jewish (ASJ)

AF:

0.837

AC:

18986

AN:

22690

East Asian (EAS)

AF:

0.912

AC:

33970

AN:

37258

South Asian (SAS)

AF:

0.847

AC:

61623

AN:

72728

European-Finnish (FIN)

AF:

0.842

AC:

43778

AN:

51980

Middle Eastern (MID)

AF:

0.798

AC:

3328

AN:

4172

European-Non Finnish (NFE)

AF:

0.836

AC:

607773

AN:

726664

Other (OTH)

AF:

0.829

AC:

37526

AN:

45270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

5951

11902

17852

23803

29754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11296

22592

33888

45184

56480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.797

AC:

121287

AN:

152142

Hom.:

48841

Cov.:

AF XY:

0.799

AC XY:

59426

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.664

AC:

27538

AN:

41458

American (AMR)

AF:

0.864

AC:

13224

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.844

AC:

2928

AN:

3468

East Asian (EAS)

AF:

0.895

AC:

4632

AN:

5178

South Asian (SAS)

AF:

0.835

AC:

4034

AN:

4830

European-Finnish (FIN)

AF:

0.847

AC:

8958

AN:

10576

Middle Eastern (MID)

AF:

0.837

AC:

246

AN:

294

European-Non Finnish (NFE)

AF:

0.843

AC:

57344

AN:

68010

Other (OTH)

AF:

0.799

AC:

1688

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1206

2412

3619

4825

6031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<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:

0.819

Hom.:

13786

Bravo

AF:

0.794

Asia WGS

AF:

0.822

AC:

2853

AN:

3470

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Hereditary factor X deficiency disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.70

(source)

DANN

Benign

0.68

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over