1-197065696-T-G

Position:

• chr1-197065696-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001994.3(F13B):​c.64+1464A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,018 control chromosomes in the GnomAD database, including 17,212 homozygotes. 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 0.46 (17212 hom., cov: 32)
• Consequence: F13B NM_001994.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.484

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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.64+1464A>C		intron_variant		ENST00000367412.2	NP_001985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F13B	ENST00000367412.2	c.64+1464A>C		intron_variant		1	NM_001994.3	ENSP00000356382	P1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69388 AN: 151900 Hom.: 17195 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.465

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.457 AC: 69455 AN: 152018 Hom.: 17212 Cov.: 32 AF XY: 0.467 AC XY: 34677 AN XY: 74296

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.469

Alfa AF: 0.325 Hom.: 1046

Bravo AF: 0.456

Asia WGS AF: 0.708 AC: 2458 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.47

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: rs2298882; hg19: chr1-197034826;