4-186271327-T-C

Position:

• chr4-186271327-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000128.4(F11):​c.56-282T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,080 control chromosomes in the GnomAD database, including 25,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.57 (25471 hom., cov: 32)
• Consequence: F11 NM_000128.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.295

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 4-186271327-T-C is Benign according to our data. Variant chr4-186271327-T-C is described in ClinVar as [Benign]. Clinvar id is 1262979.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.56-282T>C		intron_variant		ENST00000403665.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F11	ENST00000403665.7	c.56-282T>C		intron_variant		1	NM_000128.4	P1
F11	ENST00000492972.6	c.56-282T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87161 AN: 151962 Hom.: 25435 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.574 AC: 87245 AN: 152080 Hom.: 25471 Cov.: 32 AF XY: 0.575 AC XY: 42781 AN XY: 74338

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.527

Gnomad4 OTH AF: 0.581

Alfa AF: 0.531 Hom.: 36212

Bravo AF: 0.575

Asia WGS AF: 0.637 AC: 2219 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.59

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: rs2036914; hg19: chr4-187192481;