1-197065696-T-G

Variant names:

• chr1-197065696-T-G
• rs2298882
• NM_001994.3:c.64+1464A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• factor XIII, b subunit, deficiency of

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• congenital factor XIII deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001994.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F13B	NM_001994.3	MANE Select	c.64+1464A>C		intron	N/A	NP_001985.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F13B	ENST00000367412.2	TSL:1 MANE Select	c.64+1464A>C		intron	N/A	ENSP00000356382.2

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

African (AFR) AF: 0.285 AC: 11808 AN: 41454

American (AMR) AF: 0.595 AC: 9073 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1748 AN: 3468

East Asian (EAS) AF: 0.821 AC: 4238 AN: 5164

South Asian (SAS) AF: 0.604 AC: 2919 AN: 4832

European-Finnish (FIN) AF: 0.556 AC: 5869 AN: 10560

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32178 AN: 67970

Other (OTH) AF: 0.469 AC: 991 AN: 2114

Alfa AF: 0.323 Hom.: 1085

Bravo AF: 0.456

Asia WGS AF: 0.708 AC: 2458 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.47
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2298882; hg19: chr1-197034826;