4-186266907-T-C

Position:

• chr4-186266907-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.-1-229T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,906 control chromosomes in the GnomAD database, including 3,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (3970 hom., cov: 31)
• Consequence: F11 NM_000128.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0450

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=-0.82).
• BP6: Variant 4-186266907-T-C is Benign according to our data. Variant chr4-186266907-T-C is described in ClinVar as [Benign]. Clinvar id is 1256821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F11	NM_000128.4	c.-1-229T>C		intron_variant		ENST00000403665.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F11	ENST00000403665.7	c.-1-229T>C		intron_variant		1	NM_000128.4	P1
F11	ENST00000492972.6	c.-1-229T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33564 AN: 151788 Hom.: 3968 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.221 AC: 33593 AN: 151906 Hom.: 3970 Cov.: 31 AF XY: 0.218 AC XY: 16188 AN XY: 74250

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.262

Alfa AF: 0.231 Hom.: 644

Bravo AF: 0.230

Asia WGS AF: 0.214 AC: 745 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 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.2
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: rs4253398; hg19: chr4-187188061;