rs3822058

Variant names:

• chr4-186285026-G-A
• rs3822058
• NM_000128.4:c.1305-612G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-186285026-G-A
• chr4-186285026-G-T

Variant summary

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

The NM_000128.4(F11):​c.1305-612G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,952 control chromosomes in the GnomAD database, including 12,599 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 0.40 (12599 hom., cov: 32)
• Consequence: F11 NM_000128.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• Publications: 10 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: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F11	NM_000128.4	c.1305-612G>A		intron_variant	Intron 11 of 14	ENST00000403665.7	NP_000119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F11	ENST00000403665.7	c.1305-612G>A		intron_variant	Intron 11 of 14	1	NM_000128.4	ENSP00000384957.2

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60160 AN: 151834 Hom.: 12578 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.396 AC: 60219 AN: 151952 Hom.: 12599 Cov.: 32 AF XY: 0.392 AC XY: 29087 AN XY: 74268

African (AFR) AF: 0.509 AC: 21073 AN: 41412

American (AMR) AF: 0.366 AC: 5587 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1582 AN: 3468

East Asian (EAS) AF: 0.156 AC: 808 AN: 5176

South Asian (SAS) AF: 0.371 AC: 1781 AN: 4802

European-Finnish (FIN) AF: 0.281 AC: 2960 AN: 10550

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 24985 AN: 67982

Other (OTH) AF: 0.411 AC: 866 AN: 2106

Alfa AF: 0.377 Hom.: 10979

Bravo AF: 0.408

Asia WGS AF: 0.289 AC: 1009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.42
PhyloP100		-0.049
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: rs3822058; hg19: chr4-187206180;