chr1-197050892-G-T

Position:

chr1-197050892-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001994.3(F13B):c.1556-13C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,607,192 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0011 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 16 hom. )

Consequence

F13B
NM_001994.3 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.315

Variant links:

Genes affected

F13B (HGNC:3534): (coagulation factor XIII B chain) This gene encodes coagulation factor XIII B subunit. Coagulation factor XIII is the last zymogen to become activated in the blood coagulation cascade. Plasma factor XIII is a heterotetramer composed of 2 A subunits and 2 B subunits. The A subunits have catalytic function, and the B subunits do not have enzymatic activity and may serve as a plasma carrier molecules. Platelet factor XIII is comprised only of 2 A subunits, which are identical to those of plasma origin. Upon activation by the cleavage of the activation peptide by thrombin and in the presence of calcium ion, the plasma factor XIII dissociates its B subunits and yields the same active enzyme, factor XIIIa, as platelet factor XIII. This enzyme acts as a transglutaminase to catalyze the formation of gamma-glutamyl-epsilon-lysine crosslinking between fibrin molecules, thus stabilizing the fibrin clot. Factor XIII deficiency is classified into two categories: type I deficiency, characterized by the lack of both the A and B subunits; and type II deficiency, characterized by the lack of the A subunit alone. These defects can result in a lifelong bleeding tendency, defective wound healing, and habitual abortion. [provided by RefSeq, Jul 2008]

F13B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 1-197050892-G-T is Benign according to our data. Variant chr1-197050892-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 258503.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00108 (164/152270) while in subpopulation SAS AF= 0.0122 (59/4828). AF 95% confidence interval is 0.00973. There are 3 homozygotes in gnomad4. There are 99 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F13B	NM_001994.3 link	c.1556-13C>A		intron_variant		ENST00000367412.2	NP_001985.2	P05160

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
F13B	ENST00000367412.2 link	c.1556-13C>A	intron_variant	1	NM_001994.3	ENSP00000356382.2	P05160
F13B	ENST00000649282.1 link	c.311-13C>A	intron_variant			ENSP00000497116.1	A0A3B3IS66
F13B	ENST00000490002.1 link	n.-47C>A	upstream_gene_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00107

AC:

163

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00231

AC:

574

AN:

248876

Hom.:

AF XY:

0.00289

AC XY:

389

AN XY:

134586

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.000350

Gnomad ASJ exome

AF:

0.00789

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0110

Gnomad FIN exome

AF:

0.0000936

Gnomad NFE exome

AF:

0.00114

Gnomad OTH exome

AF:

0.00231

GnomAD4 exome

AF:

0.00149

AC:

2162

AN:

1454922

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1320

AN XY:

724160

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000337

Gnomad4 ASJ exome

AF:

0.00841

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0108

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.000741

Gnomad4 OTH exome

AF:

0.00210

GnomAD4 genome

AF:

0.00108

AC:

164

AN:

152270

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.000744

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Factor XIII, b subunit, deficiency of

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

8.5

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over