rs4241824

Variant names:

• chr4-186270633-G-A
• rs4241824
• NM_000128.4:c.56-976G>A

Variant summary

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

The NM_000128.4(F11):​c.56-976G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 150,790 control chromosomes in the GnomAD database, including 23,225 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 0.55 (23225 hom., cov: 29)
• Consequence: F11 NM_000128.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F11	NM_000128.4	c.56-976G>A		intron_variant	Intron 2 of 14	ENST00000403665.7	NP_000119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F11	ENST00000403665.7	c.56-976G>A		intron_variant	Intron 2 of 14	1	NM_000128.4	ENSP00000384957.2
F11	ENST00000492972.6	c.56-976G>A		intron_variant	Intron 2 of 4	2		ENSP00000424479.1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 82973 AN: 150674 Hom.: 23191 Cov.: 29

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.551 AC: 83056 AN: 150790 Hom.: 23225 Cov.: 29 AF XY: 0.553 AC XY: 40713 AN XY: 73622

African (AFR) AF: 0.621 AC: 25531 AN: 41090

American (AMR) AF: 0.545 AC: 8194 AN: 15048

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1471 AN: 3458

East Asian (EAS) AF: 0.776 AC: 3973 AN: 5120

South Asian (SAS) AF: 0.459 AC: 2160 AN: 4710

European-Finnish (FIN) AF: 0.602 AC: 6261 AN: 10408

Middle Eastern (MID) AF: 0.431 AC: 125 AN: 290

European-Non Finnish (NFE) AF: 0.498 AC: 33736 AN: 67686

Other (OTH) AF: 0.553 AC: 1147 AN: 2074

Alfa AF: 0.503 Hom.: 9355

Bravo AF: 0.548

Asia WGS AF: 0.626 AC: 2178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.66
PhyloP100		0.13
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: rs4241824; hg19: chr4-187191787;