rs698859

Variant names:

• chr1-197039235-C-T
• rs698859
• NM_001994.3:c.*143G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-197039235-C-T
• chr1-197039235-C-A

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.*143G>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 0.363 in 670,238 control chromosomes in the GnomAD database, including 48,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9112 hom., cov: 32)
  • Exomes 𝑓: 0.38 (39137 hom.)
• Consequence: F13B NM_001994.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.130
• Publications: 9 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-197039235-C-T is Benign according to our data. Variant chr1-197039235-C-T is described in ClinVar as Benign. ClinVar VariationId is 294566.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F13B	NM_001994.3	MANE Select	c.*143G>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.*143G>A		3_prime_UTR	Exon 12 of 12	ENSP00000356382.2	P05160
	F13B	ENST00000895404.1		c.*143G>A		3_prime_UTR	Exon 11 of 11	ENSP00000565463.1
	F13B	ENST00000895399.1		c.*143G>A		3_prime_UTR	Exon 11 of 11	ENSP00000565458.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48476 AN: 151644 Hom.: 9113 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.376 AC: 194771 AN: 518472 Hom.: 39137 Cov.: 7 AF XY: 0.376 AC XY: 105155 AN XY: 279788

African (AFR) AF: 0.138 AC: 1879 AN: 13650

American (AMR) AF: 0.225 AC: 5575 AN: 24760

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 5884 AN: 15140

East Asian (EAS) AF: 0.155 AC: 5084 AN: 32848

South Asian (SAS) AF: 0.303 AC: 13902 AN: 45888

European-Finnish (FIN) AF: 0.370 AC: 13368 AN: 36104

Middle Eastern (MID) AF: 0.371 AC: 764 AN: 2058

European-Non Finnish (NFE) AF: 0.431 AC: 138145 AN: 320502

Other (OTH) AF: 0.370 AC: 10170 AN: 27522

GnomAD4 genome AF: 0.319 AC: 48485 AN: 151766 Hom.: 9112 Cov.: 32 AF XY: 0.315 AC XY: 23360 AN XY: 74150

African (AFR) AF: 0.144 AC: 5955 AN: 41420

American (AMR) AF: 0.274 AC: 4177 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1382 AN: 3466

East Asian (EAS) AF: 0.163 AC: 843 AN: 5174

South Asian (SAS) AF: 0.294 AC: 1418 AN: 4816

European-Finnish (FIN) AF: 0.373 AC: 3914 AN: 10502

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29585 AN: 67828

Other (OTH) AF: 0.339 AC: 716 AN: 2110

Alfa AF: 0.406 Hom.: 14643

Bravo AF: 0.301

Asia WGS AF: 0.205 AC: 714 AN: 3466

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Factor XIII, b subunit, deficiency of (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.8
DANN	Benign	0.63
PhyloP100		0.13
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: rs698859; hg19: chr1-197008365; COSMIC: COSV66372965; COSMIC: COSV66372965;