rs2289252

Variant names:

• chr4-186286227-C-T
• rs2289252
• ENST00000505103.5:n.1045G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000505103.5(F11-AS1):​n.1045G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 591,776 control chromosomes in the GnomAD database, including 41,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9788 hom., cov: 31)
  • Exomes 𝑓: 0.38 (32014 hom.)
• Consequence: F11-AS1 ENST00000505103.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.23
• Publications: 87 publications found

Genes affected

F11-AS1 (HGNC:27725): (F11 antisense RNA 1)

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 4-186286227-C-T is Benign according to our data. Variant chr4-186286227-C-T is described in ClinVar as Benign. ClinVar VariationId is 760971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F11	NM_000128.4	c.1481-188C>T		intron_variant	Intron 12 of 14	ENST00000403665.7	NP_000119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F11-AS1	ENST00000505103.5	n.1045G>A		non_coding_transcript_exon_variant	Exon 4 of 4	1
F11	ENST00000403665.7	c.1481-188C>T		intron_variant	Intron 12 of 14	1	NM_000128.4	ENSP00000384957.2
F11	ENST00000264691.4	c.175+414C>T		intron_variant	Intron 1 of 2	3		ENSP00000264691.4

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53736 AN: 151842 Hom.: 9777 Cov.: 31

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.377 AC: 165709 AN: 439816 Hom.: 32014 Cov.: 5 AF XY: 0.373 AC XY: 87522 AN XY: 234944

African (AFR) AF: 0.255 AC: 3289 AN: 12910

American (AMR) AF: 0.353 AC: 8593 AN: 24334

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 4804 AN: 13538

East Asian (EAS) AF: 0.333 AC: 8919 AN: 26810

South Asian (SAS) AF: 0.301 AC: 14787 AN: 49046

European-Finnish (FIN) AF: 0.422 AC: 9860 AN: 23366

Middle Eastern (MID) AF: 0.325 AC: 594 AN: 1828

European-Non Finnish (NFE) AF: 0.401 AC: 105864 AN: 263712

Other (OTH) AF: 0.371 AC: 8999 AN: 24272

GnomAD4 genome AF: 0.354 AC: 53771 AN: 151960 Hom.: 9788 Cov.: 31 AF XY: 0.352 AC XY: 26105 AN XY: 74252

African (AFR) AF: 0.259 AC: 10721 AN: 41430

American (AMR) AF: 0.359 AC: 5473 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1212 AN: 3468

East Asian (EAS) AF: 0.349 AC: 1803 AN: 5164

South Asian (SAS) AF: 0.311 AC: 1495 AN: 4806

European-Finnish (FIN) AF: 0.409 AC: 4305 AN: 10532

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.403 AC: 27422 AN: 67984

Other (OTH) AF: 0.386 AC: 815 AN: 2114

Alfa AF: 0.383 Hom.: 45596

Bravo AF: 0.347

Asia WGS AF: 0.343 AC: 1193 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 26423325) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.090
DANN	Benign	0.68
PhyloP100		-1.2
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: rs2289252; hg19: chr4-187207381;