rs78780803

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.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. 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. S543N) has been classified as Uncertain significance.

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

Publications

10 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=0.001069814).

BP6

Variant 11-118902116-T-C is Benign according to our data. Variant chr11-118902116-T-C is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
BCL9L	NM_001378213.1 link	c.1627A>G	p.Ser543Gly	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.1627A>G	p.Ser543Gly	missense_variant	Exon 8 of 10		NM_001378213.1	ENSP00000507778.1	Q86UU0-1
BCL9L	ENST00000334801.7 link	c.1627A>G	p.Ser543Gly	missense_variant	Exon 6 of 8	1		ENSP00000335320.3	Q86UU0-1
BCL9L	ENST00000526143.2 link	c.1516A>G	p.Ser506Gly	missense_variant	Exon 6 of 8	5		ENSP00000482938.1	A0A087WZX0
BCL9L	ENST00000530293.1 link	n.41-1355A>G		intron_variant	Intron 1 of 2	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

GnomAD2 exomes

AF:

0.0218

AC:

5470

AN:

251150

AF XY:

0.0208

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 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

African (AFR)

AF:

0.0355

AC:

1190

AN:

33480

American (AMR)

AF:

0.00461

AC:

206

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00352

AC:

AN:

26136

East Asian (EAS)

AF:

0.0910

AC:

3613

AN:

39700

South Asian (SAS)

AF:

0.0163

AC:

1410

AN:

86252

European-Finnish (FIN)

AF:

0.0422

AC:

2254

AN:

53366

Middle Eastern (MID)

AF:

0.00659

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00758

AC:

8425

AN:

1111998

Other (OTH)

AF:

0.0174

AC:

1053

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

1126

2251

3377

4502

5628

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.0224

AC:

3413

AN:

152086

Hom.:

Cov.:

AF XY:

0.0242

AC XY:

1797

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0366

AC:

1518

AN:

41484

American (AMR)

AF:

0.00856

AC:

131

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3468

East Asian (EAS)

AF:

0.114

AC:

583

AN:

5136

South Asian (SAS)

AF:

0.0166

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0495

AC:

524

AN:

10596

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00777

AC:

528

AN:

67980

Other (OTH)

AF:

0.0133

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

168

336

504

672

840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0132

Hom.:

113

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

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

0.050

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

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;.

PhyloP100

1.9

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

Mutation Taster

=99/1

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