1-197039289-C-G

Position:

• chr1-197039289-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000367412.2(F13B):​c.*89G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,140,274 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (51 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (38 hom.)
• Consequence: F13B ENST00000367412.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.463

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=-0.86).
• BP6: Variant 1-197039289-C-G is Benign according to our data. Variant chr1-197039289-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 294567.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0152 (2309/152068) while in subpopulation AFR AF= 0.0494 (2048/41494). AF 95% confidence interval is 0.0476. There are 51 homozygotes in gnomad4. There are 1117 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F13B	NM_001994.3	c.*89G>C		3_prime_UTR_variant	12/12	ENST00000367412.2	NP_001985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F13B	ENST00000367412.2	c.*89G>C		3_prime_UTR_variant	12/12	1	NM_001994.3	ENSP00000356382	P1
F13B	ENST00000649282.1	c.*89G>C		3_prime_UTR_variant	5/5			ENSP00000497116

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2303 AN: 151950 Hom.: 51 Cov.: 33

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00675

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0203

Gnomad SAS AF: 0.00208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.00907

GnomAD4 exome AF: 0.00236 AC: 2333 AN: 988206 Hom.: 38 Cov.: 13 AF XY: 0.00213 AC XY: 1088 AN XY: 509832

Gnomad4 AFR exome AF: 0.0476

Gnomad4 AMR exome AF: 0.00316

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0173

Gnomad4 SAS exome AF: 0.000830

Gnomad4 FIN exome AF: 0.0000402

Gnomad4 NFE exome AF: 0.000247

Gnomad4 OTH exome AF: 0.00516

GnomAD4 genome AF: 0.0152 AC: 2309 AN: 152068 Hom.: 51 Cov.: 33 AF XY: 0.0150 AC XY: 1117 AN XY: 74330

Gnomad4 AFR AF: 0.0494

Gnomad4 AMR AF: 0.00674

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0201

Gnomad4 SAS AF: 0.00208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.000707 Hom.: 0

Bravo AF: 0.0162

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Factor XIII, b subunit, deficiency of Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.76
DANN	Benign	0.11

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: rs17549873; hg19: chr1-197008419;