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GeneBe

rs61730467

chr11-118901451-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001378213.1(BCL9L):c.2292C>T(p.Pro764=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 1,614,072 control chromosomes in the GnomAD database, including 1,251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.037 ( 131 hom., cov: 32)
Exomes 𝑓: 0.032 ( 1120 hom. )

Consequence

BCL9L
NM_001378213.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.500
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-118901451-G-A is Benign according to our data. Variant chr11-118901451-G-A is described in ClinVar as [Benign]. Clinvar id is 402415.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.5 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0841 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BCL9LNM_001378213.1 linkuse as main transcriptc.2292C>T p.Pro764= synonymous_variant 8/10 ENST00000683865.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BCL9LENST00000683865.1 linkuse as main transcriptc.2292C>T p.Pro764= synonymous_variant 8/10 NM_001378213.1 P4Q86UU0-1
BCL9LENST00000334801.7 linkuse as main transcriptc.2292C>T p.Pro764= synonymous_variant 6/81 P4Q86UU0-1
BCL9LENST00000526143.2 linkuse as main transcriptc.2181C>T p.Pro727= synonymous_variant 6/85 A1
BCL9LENST00000530293.1 linkuse as main transcriptn.41-690C>T intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0374
AC:
5698
AN:
152166
Hom.:
132
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0507
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0426
Gnomad ASJ
AF:
0.0548
Gnomad EAS
AF:
0.00193
Gnomad SAS
AF:
0.0913
Gnomad FIN
AF:
0.0206
Gnomad MID
AF:
0.0823
Gnomad NFE
AF:
0.0285
Gnomad OTH
AF:
0.0592
GnomAD3 exomes
AF:
0.0374
AC:
9383
AN:
251032
Hom.:
289
AF XY:
0.0409
AC XY:
5555
AN XY:
135702
show subpopulations
Gnomad AFR exome
AF:
0.0500
Gnomad AMR exome
AF:
0.0291
Gnomad ASJ exome
AF:
0.0572
Gnomad EAS exome
AF:
0.00343
Gnomad SAS exome
AF:
0.0954
Gnomad FIN exome
AF:
0.0186
Gnomad NFE exome
AF:
0.0293
Gnomad OTH exome
AF:
0.0455
GnomAD4 exome
AF:
0.0317
AC:
46267
AN:
1461788
Hom.:
1120
Cov.:
36
AF XY:
0.0337
AC XY:
24522
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.0564
Gnomad4 AMR exome
AF:
0.0318
Gnomad4 ASJ exome
AF:
0.0553
Gnomad4 EAS exome
AF:
0.00159
Gnomad4 SAS exome
AF:
0.0919
Gnomad4 FIN exome
AF:
0.0212
Gnomad4 NFE exome
AF:
0.0266
Gnomad4 OTH exome
AF:
0.0393
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0375
AC:
5704
AN:
152284
Hom.:
131
Cov.:
32
AF XY:
0.0378
AC XY:
2814
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0508
Gnomad4 AMR
AF:
0.0425
Gnomad4 ASJ
AF:
0.0548
Gnomad4 EAS
AF:
0.00193
Gnomad4 SAS
AF:
0.0912
Gnomad4 FIN
AF:
0.0206
Gnomad4 NFE
AF:
0.0285
Gnomad4 OTH
AF:
0.0586
Alfa
AF:
0.0345
Hom.:
54
Bravo
AF:
0.0390
Asia WGS
AF:
0.0460
AC:
160
AN:
3478
EpiCase
AF:
0.0335
EpiControl
AF:
0.0358

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant 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: MAF -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
2.8
Dann
Benign
0.85
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.

Other links and lift over

dbSNP: rs61730467; hg19: chr11-118772160; COSMIC: COSV52689779; COSMIC: COSV52689779; API