Variant chr4-186286381-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000128.4(F11):c.1481-34G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.053 in 1,539,260 control chromosomes in the GnomAD database, including 2,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.069 ( 473 hom., cov: 32)

Exomes 𝑓: 0.051 ( 2216 hom. )

Consequence

F11
NM_000128.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.161

Variant links:

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 links:

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

F11-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 4-186286381-G-T is Benign according to our data. Variant chr4-186286381-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1185147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F11	NM_000128.4 linkuse as main transcript	c.1481-34G>T		intron_variant		ENST00000403665.7	NP_000119.1
F11-AS1	NR_033900.1 linkuse as main transcript	n.1067-115C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
F11	ENST00000403665.7 linkuse as main transcript	c.1481-34G>T	intron_variant	1	NM_000128.4	ENSP00000384957	P1	P03951-1
F11-AS1	ENST00000505103.5 linkuse as main transcript	n.1006-115C>A	intron_variant, non_coding_transcript_variant	1
F11	ENST00000264691.4 linkuse as main transcript	c.176+568G>T	intron_variant	3		ENSP00000264691

Frequencies

GnomAD3 genomes

AF:

0.0692

AC:

10519

AN:

152080

Hom.:

466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.0815

Gnomad AMR

AF:

0.0605

Gnomad ASJ

AF:

0.0816

Gnomad EAS

AF:

0.0669

Gnomad SAS

AF:

0.0784

Gnomad FIN

AF:

0.0379

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.0461

Gnomad OTH

AF:

0.0556

GnomAD3 exomes

AF:

0.0608

AC:

15269

AN:

250968

Hom.:

582

AF XY:

0.0604

AC XY:

8195

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.0710

Gnomad ASJ exome

AF:

0.0816

Gnomad EAS exome

AF:

0.0696

Gnomad SAS exome

AF:

0.0765

Gnomad FIN exome

AF:

0.0386

Gnomad NFE exome

AF:

0.0463

Gnomad OTH exome

AF:

0.0593

GnomAD4 exome

AF:

0.0512

AC:

71051

AN:

1387062

Hom.:

2216

Cov.:

AF XY:

0.0520

AC XY:

36139

AN XY:

694690

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.0702

Gnomad4 ASJ exome

AF:

0.0824

Gnomad4 EAS exome

AF:

0.0806

Gnomad4 SAS exome

AF:

0.0772

Gnomad4 FIN exome

AF:

0.0379

Gnomad4 NFE exome

AF:

0.0441

Gnomad4 OTH exome

AF:

0.0568

GnomAD4 genome

AF:

0.0693

AC:

10550

AN:

152198

Hom.:

473

Cov.:

AF XY:

0.0695

AC XY:

5168

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.0610

Gnomad4 ASJ

AF:

0.0816

Gnomad4 EAS

AF:

0.0669

Gnomad4 SAS

AF:

0.0787

Gnomad4 FIN

AF:

0.0379

Gnomad4 NFE

AF:

0.0461

Gnomad4 OTH

AF:

0.0545

Alfa

AF:

0.0370

Hom.:

Bravo

AF:

0.0733

Asia WGS

AF:

0.0530

AC:

183

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hereditary factor XI deficiency disease

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.34

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over