chr4-186264957-A-G

Variant names:

• chr4-186264957-A-G
• rs3756009
• ENST00000886339.1:c.-1-2179A>G

Variant summary

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

The ENST00000886339.1(F11):​c.-1-2179A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,046 control chromosomes in the GnomAD database, including 8,654 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 0.32 (8654 hom., cov: 32)
• Consequence: F11 ENST00000886339.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264
• Publications: 11 publications found

Genes affected

F11 (HGNC:3529): (coagulation factor XI) This gene encodes coagulation factor XI of the blood coagulation cascade. This protein is present in plasma as a zymogen, which is a unique plasma coagulation enzyme because it exists as a homodimer consisting of two identical polypeptide chains linked by disulfide bonds. During activation of the plasma factor XI, an internal peptide bond is cleaved by factor XIIa (or XII) in each of the two chains, resulting in activated factor XIa, a serine protease composed of two heavy and two light chains held together by disulfide bonds. This activated plasma factor XI triggers the middle phase of the intrisic pathway of blood coagulation by activating factor IX. Defects in this factor lead to Rosenthal syndrome, a blood coagulation abnormality. [provided by RefSeq, Jul 2008]

F11 Gene-Disease associations (from GenCC):

• congenital factor XI deficiency

  Inheritance: AD, SD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000886339.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F11	ENST00000886339.1		c.-1-2179A>G		intron	N/A	ENSP00000556398.1
	F11	ENST00000886340.1		c.-1-2179A>G		intron	N/A	ENSP00000556399.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48610 AN: 151928 Hom.: 8643 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.320 AC: 48634 AN: 152046 Hom.: 8654 Cov.: 32 AF XY: 0.320 AC XY: 23754 AN XY: 74314

African (AFR) AF: 0.152 AC: 6306 AN: 41482

American (AMR) AF: 0.356 AC: 5440 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1262 AN: 3468

East Asian (EAS) AF: 0.330 AC: 1699 AN: 5152

South Asian (SAS) AF: 0.295 AC: 1421 AN: 4822

European-Finnish (FIN) AF: 0.416 AC: 4386 AN: 10550

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26832 AN: 67976

Other (OTH) AF: 0.359 AC: 757 AN: 2108

Alfa AF: 0.363 Hom.: 27403

Bravo AF: 0.309

Asia WGS AF: 0.327 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.74
DANN	Benign	0.44
PhyloP100		-0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3756009; hg19: chr4-187186111;