rs10754210

Variant names:

• chr1-197042981-G-A
• rs10754210
• NM_001994.3:c.1739-2246C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001994.3(F13B):​c.1739-2246C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,194 control chromosomes in the GnomAD database, including 5,484 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 0.26 (5484 hom., cov: 28)
• Consequence: F13B NM_001994.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 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.1739-2246C>T		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.1739-2246C>T		intron	N/A	ENSP00000356382.2
	F13B	ENST00000649282.1		c.494-2246C>T		intron	N/A	ENSP00000497116.1
	F13B	ENST00000490002.1	TSL:3	n.150-2246C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39149 AN: 151074 Hom.: 5477 Cov.: 28

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.260

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.259 AC: 39164 AN: 151194 Hom.: 5484 Cov.: 28 AF XY: 0.257 AC XY: 18947 AN XY: 73764

African (AFR) AF: 0.159 AC: 6545 AN: 41282

American (AMR) AF: 0.254 AC: 3844 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1043 AN: 3462

East Asian (EAS) AF: 0.129 AC: 648 AN: 5012

South Asian (SAS) AF: 0.294 AC: 1400 AN: 4762

European-Finnish (FIN) AF: 0.307 AC: 3207 AN: 10430

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.315 AC: 21385 AN: 67786

Other (OTH) AF: 0.263 AC: 552 AN: 2100

Alfa AF: 0.304 Hom.: 28218

Bravo AF: 0.251

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.42
PhyloP100		0.058
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: rs10754210; hg19: chr1-197012111;