rs3756008

Variant names:

• chr4-186264231-A-T
• rs3756008
• ENST00000886339.1:c.-1-2905A>T

Variant summary

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

The ENST00000886339.1(F11):​c.-1-2905A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,054 control chromosomes in the GnomAD database, including 10,081 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 0.36 (10081 hom., cov: 32)
• Consequence: F11 ENST00000886339.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.800
• Publications: 31 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, AR, SD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.397 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.-1-2905A>T		intron	N/A	ENSP00000556398.1
	F11	ENST00000886340.1		c.-1-2905A>T		intron	N/A	ENSP00000556399.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54531 AN: 151936 Hom.: 10063 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.359 AC: 54580 AN: 152054 Hom.: 10081 Cov.: 32 AF XY: 0.358 AC XY: 26598 AN XY: 74292

African (AFR) AF: 0.269 AC: 11148 AN: 41492

American (AMR) AF: 0.369 AC: 5638 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1382 AN: 3470

East Asian (EAS) AF: 0.330 AC: 1706 AN: 5166

South Asian (SAS) AF: 0.337 AC: 1623 AN: 4820

European-Finnish (FIN) AF: 0.419 AC: 4418 AN: 10550

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.401 AC: 27285 AN: 67964

Other (OTH) AF: 0.391 AC: 827 AN: 2114

Alfa AF: 0.392 Hom.: 6815

Bravo AF: 0.350

Asia WGS AF: 0.346 AC: 1205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.46
PhyloP100		0.80

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3756008;

hg19: chr4-187185385;