Variant rs75656086 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.1272C>T(p.Ser424=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,608,966 control chromosomes in the GnomAD database, including 416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 63 hom., cov: 33)

Exomes 𝑓: 0.012 ( 353 hom. )

Consequence

BCL9L
NM_001378213.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.87

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=-0.83).

BP6

Variant 11-118902471-G-A is Benign according to our data. Variant chr11-118902471-G-A is described in ClinVar as [Benign]. Clinvar id is 402418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.87 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.106 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.1272C>T	p.Ser424=	synonymous_variant	8/10	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.1272C>T	p.Ser424=	synonymous_variant	8/10		NM_001378213.1	ENSP00000507778	P4	Q86UU0-1
BCL9L	ENST00000334801.7 linkuse as main transcript	c.1272C>T	p.Ser424=	synonymous_variant	6/8	1		ENSP00000335320	P4	Q86UU0-1
BCL9L	ENST00000526143.2 linkuse as main transcript	c.1161C>T	p.Ser387=	synonymous_variant	6/8	5		ENSP00000482938	A1
BCL9L	ENST00000530293.1 linkuse as main transcript	n.41-1710C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

2491

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00726

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.0165

Gnomad FIN

AF:

0.0490

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00763

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.0204

AC:

4940

AN:

242632

Hom.:

205

AF XY:

0.0198

AC XY:

2617

AN XY:

132380

show subpopulations

Gnomad AFR exome

AF:

0.0168

Gnomad AMR exome

AF:

0.00385

Gnomad ASJ exome

AF:

0.00473

Gnomad EAS exome

AF:

0.128

Gnomad SAS exome

AF:

0.0162

Gnomad FIN exome

AF:

0.0433

Gnomad NFE exome

AF:

0.00685

Gnomad OTH exome

AF:

0.0133

GnomAD4 exome

AF:

0.0117

AC:

17022

AN:

1456634

Hom.:

353

Cov.:

AF XY:

0.0119

AC XY:

8603

AN XY:

724606

show subpopulations

Gnomad4 AFR exome

AF:

0.0141

Gnomad4 AMR exome

AF:

0.00429

Gnomad4 ASJ exome

AF:

0.00347

Gnomad4 EAS exome

AF:

0.0905

Gnomad4 SAS exome

AF:

0.0164

Gnomad4 FIN exome

AF:

0.0411

Gnomad4 NFE exome

AF:

0.00737

Gnomad4 OTH exome

AF:

0.0161

GnomAD4 genome

AF:

0.0164

AC:

2497

AN:

152332

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1376

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0154

Gnomad4 AMR

AF:

0.00725

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.113

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.0490

Gnomad4 NFE

AF:

0.00763

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.00800

Hom.:

Bravo

AF:

0.0136

Asia WGS

AF:

0.0530

AC:

185

AN:

3478

EpiCase

AF:

0.00600

EpiControl

AF:

0.00617

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

-0.83

CADD

Benign

0.12

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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