chr1-197039235-C-T

Position:

• chr1-197039235-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001994.3(F13B):​c.*143G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 670,238 control chromosomes in the GnomAD database, including 48,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9112 hom., cov: 32)
  • Exomes 𝑓: 0.38 (39137 hom.)
• Consequence: F13B NM_001994.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.130

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-197039235-C-T is Benign according to our data. Variant chr1-197039235-C-T is described in ClinVar as [Benign]. Clinvar id is 294566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-197039235-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F13B	NM_001994.3	c.*143G>A		3_prime_UTR_variant	12/12	ENST00000367412.2	NP_001985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F13B	ENST00000367412.2	c.*143G>A		3_prime_UTR_variant	12/12	1	NM_001994.3	ENSP00000356382	P1
F13B	ENST00000649282.1	c.*143G>A		3_prime_UTR_variant	5/5			ENSP00000497116

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48476 AN: 151644 Hom.: 9113 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.376 AC: 194771 AN: 518472 Hom.: 39137 Cov.: 7 AF XY: 0.376 AC XY: 105155 AN XY: 279788

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.225

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.303

Gnomad4 FIN exome AF: 0.370

Gnomad4 NFE exome AF: 0.431

Gnomad4 OTH exome AF: 0.370

GnomAD4 genome AF: 0.319 AC: 48485 AN: 151766 Hom.: 9112 Cov.: 32 AF XY: 0.315 AC XY: 23360 AN XY: 74150

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.339

Alfa AF: 0.410 Hom.: 12423

Bravo AF: 0.301

Asia WGS AF: 0.205 AC: 714 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Factor XIII, b subunit, deficiency of Benign:1

Benign, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.8
DANN	Benign	0.63

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: rs698859; hg19: chr1-197008365; COSMIC: COSV66372965; COSMIC: COSV66372965;