rs4241824

chr4-186270633-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
F11	NM_000128.4	c.56-976G>A		intron_variant		ENST00000403665.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F11	ENST00000403665.7	c.56-976G>A		intron_variant		1	NM_000128.4	P1
F11	ENST00000492972.6	c.56-976G>A		intron_variant		2

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

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.776

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.553

Alfa AF: 0.502 Hom.: 8232

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4241824; hg19: chr4-187191787;