rs5990

Positions:

• chr1-197039467-A-C
• chr1-197039467-A-G
• chr1-197039467-A-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.1953-56T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,410,192 control chromosomes in the GnomAD database, including 179,483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16594 hom., cov: 32)
  • Exomes 𝑓: 0.50 (162889 hom.)
• Consequence: F13B NM_001994.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.503

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=-0.88).
• BP6: Variant 1-197039467-A-C is Benign according to our data. Variant chr1-197039467-A-C is described in ClinVar as [Benign]. Clinvar id is 1270193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F13B	NM_001994.3	c.1953-56T>G		intron_variant		ENST00000367412.2	NP_001985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F13B	ENST00000367412.2	c.1953-56T>G		intron_variant		1	NM_001994.3	ENSP00000356382	P1
F13B	ENST00000649282.1	c.708-56T>G		intron_variant				ENSP00000497116

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67095 AN: 151716 Hom.: 16582 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.499 AC: 628409 AN: 1258356 Hom.: 162889 AF XY: 0.502 AC XY: 319046 AN XY: 635786

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.708

Gnomad4 ASJ exome AF: 0.493

Gnomad4 EAS exome AF: 0.829

Gnomad4 SAS exome AF: 0.589

Gnomad4 FIN exome AF: 0.563

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.442 AC: 67128 AN: 151836 Hom.: 16594 Cov.: 32 AF XY: 0.452 AC XY: 33545 AN XY: 74168

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.462

Alfa AF: 0.433 Hom.: 2224

Bravo AF: 0.439

Asia WGS AF: 0.699 AC: 2417 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.45

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: rs5990; hg19: chr1-197008597; COSMIC: COSV66375848; COSMIC: COSV66375848;