rs78780803

Positions:

Variant summary

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

The NM_001378213.1(BCL9L):c.1627A>G(p.Ser543Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,902 control chromosomes in the GnomAD database, including 467 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 86 hom., cov: 32)

Exomes 𝑓: 0.013 ( 381 hom. )

Consequence

BCL9L
NM_001378213.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.92

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001069814).

BP6

Variant 11-118902116-T-C is Benign according to our data. Variant chr11-118902116-T-C is described in ClinVar as [Benign]. Clinvar id is 402417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.1627A>G	p.Ser543Gly	missense_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.1627A>G	p.Ser543Gly	missense_variant	8/10		NM_001378213.1	ENSP00000507778	P4	Q86UU0-1
BCL9L	ENST00000334801.7 linkuse as main transcript	c.1627A>G	p.Ser543Gly	missense_variant	6/8	1		ENSP00000335320	P4	Q86UU0-1
BCL9L	ENST00000526143.2 linkuse as main transcript	c.1516A>G	p.Ser506Gly	missense_variant	6/8	5		ENSP00000482938	A1
BCL9L	ENST00000530293.1 linkuse as main transcript	n.41-1355A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0224

AC:

3403

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0364

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00857

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.0495

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00777

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0218

AC:

5470

AN:

251150

Hom.:

218

AF XY:

0.0208

AC XY:

2823

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.0368

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.00477

Gnomad EAS exome

AF:

0.129

Gnomad SAS exome

AF:

0.0162

Gnomad FIN exome

AF:

0.0443

Gnomad NFE exome

AF:

0.00703

Gnomad OTH exome

AF:

0.0129

GnomAD4 exome

AF:

0.0125

AC:

18281

AN:

1461816

Hom.:

381

Cov.:

AF XY:

0.0126

AC XY:

9134

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0355

Gnomad4 AMR exome

AF:

0.00461

Gnomad4 ASJ exome

AF:

0.00352

Gnomad4 EAS exome

AF:

0.0910

Gnomad4 SAS exome

AF:

0.0163

Gnomad4 FIN exome

AF:

0.0422

Gnomad4 NFE exome

AF:

0.00758

Gnomad4 OTH exome

AF:

0.0174

GnomAD4 genome

AF:

0.0224

AC:

3413

AN:

152086

Hom.:

Cov.:

AF XY:

0.0242

AC XY:

1797

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0366

Gnomad4 AMR

AF:

0.00856

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.0166

Gnomad4 FIN

AF:

0.0495

Gnomad4 NFE

AF:

0.00777

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.0118

Hom.:

Bravo

AF:

0.0206

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.0370

AC:

163

ESP6500EA

AF:

0.00733

AC:

ExAC

AF:

0.0206

AC:

2506

Asia WGS

AF:

0.0550

AC:

189

AN:

3478

EpiCase

AF:

0.00616

EpiControl

AF:

0.00611

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

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.082

T;.

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.25

T;T

MetaRNN

Benign

0.0011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

N;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.36

N;.

REVEL

Benign

0.11

Sift

Benign

0.40

T;.

Sift4G

Benign

0.62

T;T

Polyphen

0.0

B;.

Vest4

0.083

MPC

0.18

ClinPred

0.000036

GERP RS

4.6

Varity_R

0.030

gMVP

0.12

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