11-118901807-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378213.1(BCL9L):c.1936A>G(p.Met646Val) variant causes a missense change. The variant allele was found at a frequency of 0.0115 in 1,610,672 control chromosomes in the GnomAD database, including 398 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M646L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.013 ( 53 hom., cov: 32)

Exomes 𝑓: 0.011 ( 345 hom. )

Consequence

BCL9L
NM_001378213.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.54

Publications

6 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014236867).

BP6

Variant 11-118901807-T-C is Benign according to our data. Variant chr11-118901807-T-C is described in ClinVar as [Benign]. Clinvar id is 402416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL9L	NM_001378213.1 link	c.1936A>G	p.Met646Val	missense_variant	Exon 8 of 10	ENST00000683865.1	NP_001365142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BCL9L	ENST00000683865.1 link	c.1936A>G	p.Met646Val	missense_variant	Exon 8 of 10		NM_001378213.1	ENSP00000507778.1	Q86UU0-1
BCL9L	ENST00000334801.7 link	c.1936A>G	p.Met646Val	missense_variant	Exon 6 of 8	1		ENSP00000335320.3	Q86UU0-1
BCL9L	ENST00000526143.2 link	c.1825A>G	p.Met609Val	missense_variant	Exon 6 of 8	5		ENSP00000482938.1	A0A087WZX0
BCL9L	ENST00000530293.1 link	n.41-1046A>G		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1928

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.0166

Gnomad FIN

AF:

0.0491

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00762

Gnomad OTH

AF:

0.00863

GnomAD2 exomes

AF:

0.0193

AC:

4826

AN:

250482

AF XY:

0.0190

show subpopulations

Gnomad AFR exome

AF:

0.00296

Gnomad AMR exome

AF:

0.00235

Gnomad ASJ exome

AF:

0.00481

Gnomad EAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.0436

Gnomad NFE exome

AF:

0.00692

Gnomad OTH exome

AF:

0.0116

GnomAD4 exome

AF:

0.0114

AC:

16656

AN:

1458404

Hom.:

345

Cov.:

AF XY:

0.0116

AC XY:

8438

AN XY:

724794

show subpopulations

African (AFR)

AF:

0.00138

AC:

AN:

33416

American (AMR)

AF:

0.00278

AC:

124

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.00353

AC:

AN:

26060

East Asian (EAS)

AF:

0.0910

AC:

3600

AN:

39580

South Asian (SAS)

AF:

0.0163

AC:

1407

AN:

86146

European-Finnish (FIN)

AF:

0.0416

AC:

2216

AN:

53308

Middle Eastern (MID)

AF:

0.00313

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00745

AC:

8261

AN:

1109308

Other (OTH)

AF:

0.0148

AC:

892

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1149

2298

3448

4597

5746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

384

768

1152

1536

1920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0126

AC:

1925

AN:

152268

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1111

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00221

AC:

AN:

41572

American (AMR)

AF:

0.00601

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.113

AC:

584

AN:

5172

South Asian (SAS)

AF:

0.0166

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0491

AC:

521

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00762

AC:

518

AN:

67996

Other (OTH)

AF:

0.00854

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

190

285

380

475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00923

Hom.:

Bravo

AF:

0.00937

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00432

AC:

ESP6500EA

AF:

0.00722

AC:

ExAC

AF:

0.0176

AC:

2140

Asia WGS

AF:

0.0500

AC:

174

AN:

3478

EpiCase

AF:

0.00611

EpiControl

AF:

0.00599

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.

PhyloP100

5.5

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.45

N;.

REVEL

Benign

0.14

Sift

Benign

0.051

T;.

Sift4G

Benign

0.59

T;T

Polyphen

0.0

B;.

Vest4

0.40

MPC

0.20

ClinPred

0.012

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.10

gMVP

0.33

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over