Variant rs7104819 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001378213.1(BCL9L):c.4182T>C(p.Pro1394=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,612,734 control chromosomes in the GnomAD database, including 144,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18730 hom., cov: 34)

Exomes 𝑓: 0.41 ( 126246 hom. )

Consequence

BCL9L
NM_001378213.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.65

Variant links:

Genes affected

BCL9L (HGNC:23688): (BCL9 like) Enables beta-catenin binding activity. Involved in several processes, including negative regulation of transforming growth factor beta receptor signaling pathway; positive regulation of epithelial to mesenchymal transition; and positive regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

BCL9L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 11-118898733-A-G is Benign according to our data. Variant chr11-118898733-A-G is described in ClinVar as [Benign]. Clinvar id is 402412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.65 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL9L	NM_001378213.1 linkuse as main transcript	c.4182T>C	p.Pro1394=	synonymous_variant	10/10	ENST00000683865.1	NP_001365142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL9L	ENST00000683865.1 linkuse as main transcript	c.4182T>C	p.Pro1394=	synonymous_variant	10/10		NM_001378213.1	ENSP00000507778	P4	Q86UU0-1
BCL9L	ENST00000334801.7 linkuse as main transcript	c.4182T>C	p.Pro1394=	synonymous_variant	8/8	1		ENSP00000335320	P4	Q86UU0-1
BCL9L	ENST00000526143.2 linkuse as main transcript	c.4071T>C	p.Pro1357=	synonymous_variant	8/8	5		ENSP00000482938	A1

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73359

AN:

152028

Hom.:

18679

Cov.:

show subpopulations

Gnomad AFR

AF:

0.638

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.547

Gnomad ASJ

AF:

0.442

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.415

Gnomad OTH

AF:

0.468

GnomAD3 exomes

AF:

0.428

AC:

105778

AN:

247098

Hom.:

23921

AF XY:

0.414

AC XY:

55540

AN XY:

134000

show subpopulations

Gnomad AFR exome

AF:

0.635

Gnomad AMR exome

AF:

0.580

Gnomad ASJ exome

AF:

0.434

Gnomad EAS exome

AF:

0.318

Gnomad SAS exome

AF:

0.278

Gnomad FIN exome

AF:

0.428

Gnomad NFE exome

AF:

0.411

Gnomad OTH exome

AF:

0.425

GnomAD4 exome

AF:

0.410

AC:

599451

AN:

1460588

Hom.:

126246

Cov.:

AF XY:

0.406

AC XY:

295129

AN XY:

726546

show subpopulations

Gnomad4 AFR exome

AF:

0.644

Gnomad4 AMR exome

AF:

0.577

Gnomad4 ASJ exome

AF:

0.440

Gnomad4 EAS exome

AF:

0.257

Gnomad4 SAS exome

AF:

0.280

Gnomad4 FIN exome

AF:

0.424

Gnomad4 NFE exome

AF:

0.410

Gnomad4 OTH exome

AF:

0.428

GnomAD4 genome

AF:

0.483

AC:

73456

AN:

152146

Hom.:

18730

Cov.:

AF XY:

0.481

AC XY:

35814

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.639

Gnomad4 AMR

AF:

0.548

Gnomad4 ASJ

AF:

0.442

Gnomad4 EAS

AF:

0.303

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.437

Gnomad4 NFE

AF:

0.415

Gnomad4 OTH

AF:

0.465

Alfa

AF:

0.435

Hom.:

5196

Bravo

AF:

0.501

Asia WGS

AF:

0.289

AC:

1004

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.3

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

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