chr1-197039216-G-T

Variant names:

• chr1-197039216-G-T
• rs180977741
• NM_001994.3:c.*162C>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_001994.3(F13B):​c.*162C>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 0.000993 in 624,594 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00090 (1 hom.)
• Consequence: F13B NM_001994.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.346
• Publications: 1 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• congenital factor XIII deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00127 (193/152046) while in subpopulation AFR AF = 0.00244 (101/41476). AF 95% confidence interval is 0.00205. There are 1 homozygotes in GnomAd4. There are 85 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F13B	NM_001994.3	MANE Select	c.*162C>A		3_prime_UTR	Exon 12 of 12	NP_001985.2	P05160

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F13B	ENST00000367412.2	TSL:1 MANE Select	c.*162C>A		3_prime_UTR	Exon 12 of 12	ENSP00000356382.2	P05160
	F13B	ENST00000895404.1		c.*162C>A		3_prime_UTR	Exon 11 of 11	ENSP00000565463.1
	F13B	ENST00000895399.1		c.*162C>A		3_prime_UTR	Exon 11 of 11	ENSP00000565458.1

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 193 AN: 151928 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00192

GnomAD4 exome AF: 0.000904 AC: 427 AN: 472548 Hom.: 1 Cov.: 5 AF XY: 0.000873 AC XY: 222 AN XY: 254408

African (AFR) AF: 0.00211 AC: 27 AN: 12792

American (AMR) AF: 0.000417 AC: 9 AN: 21588

Ashkenazi Jewish (ASJ) AF: 0.0158 AC: 219 AN: 13866

East Asian (EAS) AF: 0.00 AC: 0 AN: 31730

South Asian (SAS) AF: 0.0000450 AC: 2 AN: 44436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31928

Middle Eastern (MID) AF: 0.00356 AC: 7 AN: 1964

European-Non Finnish (NFE) AF: 0.000371 AC: 107 AN: 288050

Other (OTH) AF: 0.00214 AC: 56 AN: 26194

GnomAD4 genome AF: 0.00127 AC: 193 AN: 152046 Hom.: 1 Cov.: 32 AF XY: 0.00114 AC XY: 85 AN XY: 74304

African (AFR) AF: 0.00244 AC: 101 AN: 41476

American (AMR) AF: 0.000393 AC: 6 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 67964

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00139

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Factor XIII, b subunit, deficiency of (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.39
DANN	Benign	0.24
PhyloP100		-0.35

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: rs180977741; hg19: chr1-197008346;