rs2326707

Variant names:

• chr6-6157555-G-A
• rs2326707
• NM_000129.4:c.1909-5606C>T

Variant summary

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

The NM_000129.4(F13A1):​c.1909-5606C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,952 control chromosomes in the GnomAD database, including 17,997 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 0.48 (17997 hom., cov: 32)
• Consequence: F13A1 NM_000129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13
• Publications: 2 publications found

Genes affected

F13A1 (HGNC:3531): (coagulation factor XIII A chain) This gene encodes the coagulation factor XIII A 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 plasma carrier molecules. Platelet factor XIII is comprised only of 2 A subunits, which are identical to those of plasma origin. Upon 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. It also crosslinks alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin. 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]

F13A1 Gene-Disease associations (from GenCC):

• factor XIII, A subunit, deficiency of

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F13A1	NM_000129.4	c.1909-5606C>T		intron_variant	Intron 13 of 14	ENST00000264870.8	NP_000120.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F13A1	ENST00000264870.8	c.1909-5606C>T		intron_variant	Intron 13 of 14	1	NM_000129.4	ENSP00000264870.3

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73427 AN: 151834 Hom.: 17975 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.484 AC: 73498 AN: 151952 Hom.: 17997 Cov.: 32 AF XY: 0.480 AC XY: 35686 AN XY: 74274

African (AFR) AF: 0.575 AC: 23838 AN: 41442

American (AMR) AF: 0.434 AC: 6631 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1846 AN: 3468

East Asian (EAS) AF: 0.367 AC: 1895 AN: 5170

South Asian (SAS) AF: 0.494 AC: 2379 AN: 4814

European-Finnish (FIN) AF: 0.409 AC: 4304 AN: 10530

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 31000 AN: 67936

Other (OTH) AF: 0.480 AC: 1013 AN: 2112

Alfa AF: 0.464 Hom.: 2421

Bravo AF: 0.489

Asia WGS AF: 0.410 AC: 1429 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	19
DANN	Benign	0.70
PhyloP100		2.1
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: rs2326707; hg19: chr6-6157788;