1-197039467-A-C

Variant names:

• chr1-197039467-A-C
• rs5990
• NM_001994.3:c.1953-56T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 -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 rank	MANE	Protein	UniProt
F13B	NM_001994.3	c.1953-56T>G		intron_variant	Intron 11 of 11	ENST00000367412.2	NP_001985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F13B	ENST00000367412.2	c.1953-56T>G		intron_variant	Intron 11 of 11	1	NM_001994.3	ENSP00000356382.2
F13B	ENST00000649282.1	c.708-56T>G		intron_variant	Intron 4 of 4			ENSP00000497116.1

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

African (AFR) AF: 0.231 AC: 6733 AN: 29164

American (AMR) AF: 0.708 AC: 31054 AN: 43838

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 12151 AN: 24648

East Asian (EAS) AF: 0.829 AC: 31941 AN: 38538

South Asian (SAS) AF: 0.589 AC: 46906 AN: 79628

European-Finnish (FIN) AF: 0.563 AC: 29690 AN: 52762

Middle Eastern (MID) AF: 0.482 AC: 2589 AN: 5370

European-Non Finnish (NFE) AF: 0.473 AC: 440568 AN: 930826

Other (OTH) AF: 0.500 AC: 26777 AN: 53582

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

African (AFR) AF: 0.234 AC: 9714 AN: 41472

American (AMR) AF: 0.592 AC: 9021 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1689 AN: 3464

East Asian (EAS) AF: 0.821 AC: 4242 AN: 5168

South Asian (SAS) AF: 0.603 AC: 2907 AN: 4818

European-Finnish (FIN) AF: 0.556 AC: 5850 AN: 10522

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32099 AN: 67838

Other (OTH) AF: 0.462 AC: 972 AN: 2106

Alfa AF: 0.426 Hom.: 2247

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

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.45
PhyloP100		0.50
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: rs5990; hg19: chr1-197008597; COSMIC: COSV66375848; COSMIC: COSV66375848;