Variant rs61751532 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.4020G>A(p.Gln1340=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 1,613,746 control chromosomes in the GnomAD database, including 5,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 338 hom., cov: 33)

Exomes 𝑓: 0.076 ( 4871 hom. )

Consequence

BCL9L
NM_001378213.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.29

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=-0.52).

BP6

Variant 11-118898895-C-T is Benign according to our data. Variant chr11-118898895-C-T is described in ClinVar as [Benign]. Clinvar id is 402413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0801 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.4020G>A	p.Gln1340=	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.4020G>A	p.Gln1340=	synonymous_variant	10/10		NM_001378213.1	ENSP00000507778	P4	Q86UU0-1
BCL9L	ENST00000334801.7 linkuse as main transcript	c.4020G>A	p.Gln1340=	synonymous_variant	8/8	1		ENSP00000335320	P4	Q86UU0-1
BCL9L	ENST00000526143.2 linkuse as main transcript	c.3909G>A	p.Gln1303=	synonymous_variant	8/8	5		ENSP00000482938	A1

Frequencies

GnomAD3 genomes

AF:

0.0542

AC:

8249

AN:

152168

Hom.:

338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0160

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0396

Gnomad ASJ

AF:

0.0354

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.102

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0820

Gnomad OTH

AF:

0.0583

GnomAD3 exomes

AF:

0.0535

AC:

13430

AN:

250948

Hom.:

554

AF XY:

0.0529

AC XY:

7175

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.0152

Gnomad AMR exome

AF:

0.0258

Gnomad ASJ exome

AF:

0.0379

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00864

Gnomad FIN exome

AF:

0.0995

Gnomad NFE exome

AF:

0.0805

Gnomad OTH exome

AF:

0.0580

GnomAD4 exome

AF:

0.0758

AC:

110738

AN:

1461460

Hom.:

4871

Cov.:

AF XY:

0.0733

AC XY:

53265

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.0111

Gnomad4 AMR exome

AF:

0.0275

Gnomad4 ASJ exome

AF:

0.0361

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00984

Gnomad4 FIN exome

AF:

0.0966

Gnomad4 NFE exome

AF:

0.0883

Gnomad4 OTH exome

AF:

0.0659

GnomAD4 genome

AF:

0.0541

AC:

8245

AN:

152286

Hom.:

338

Cov.:

AF XY:

0.0530

AC XY:

3943

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0159

Gnomad4 AMR

AF:

0.0395

Gnomad4 ASJ

AF:

0.0354

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00828

Gnomad4 FIN

AF:

0.102

Gnomad4 NFE

AF:

0.0819

Gnomad4 OTH

AF:

0.0572

Alfa

AF:

0.0683

Hom.:

229

Bravo

AF:

0.0479

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.0721

EpiControl

AF:

0.0748

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

-0.52

CADD

Benign

4.8

DANN

Benign

0.93

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