rs61751532

Variant names:

• chr11-118898895-C-T
• rs61751532
• NM_001378213.1:c.4020G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001378213.1(BCL9L):​c.4020G>A​(p.Gln1340Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0737 in 1,613,746 control chromosomes in the GnomAD database, including 5,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (338 hom., cov: 33)
  • Exomes 𝑓: 0.076 (4871 hom.)
• Consequence: BCL9L NM_001378213.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.29
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 11-118898895-C-T is Benign according to our data. Variant chr11-118898895-C-T is described in ClinVar as [Benign]. Clinvar id is 402413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.29 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL9L	NM_001378213.1	c.4020G>A	p.Gln1340Gln	synonymous_variant	Exon 10 of 10	ENST00000683865.1	NP_001365142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL9L	ENST00000683865.1	c.4020G>A	p.Gln1340Gln	synonymous_variant	Exon 10 of 10		NM_001378213.1	ENSP00000507778.1
BCL9L	ENST00000334801.7	c.4020G>A	p.Gln1340Gln	synonymous_variant	Exon 8 of 8	1		ENSP00000335320.3
BCL9L	ENST00000526143.2	c.3909G>A	p.Gln1303Gln	synonymous_variant	Exon 8 of 8	5		ENSP00000482938.1

Frequencies

GnomAD3 genomes AF: 0.0542 AC: 8249 AN: 152168 Hom.: 338 Cov.: 33

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0396

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00827

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0820

Gnomad OTH AF: 0.0583

GnomAD2 exomes AF: 0.0535 AC: 13430 AN: 250948 AF XY: 0.0529

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.0258

Gnomad ASJ exome AF: 0.0379

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0995

Gnomad NFE exome AF: 0.0805

Gnomad OTH exome AF: 0.0580

GnomAD4 exome AF: 0.0758 AC: 110738 AN: 1461460 Hom.: 4871 Cov.: 65 AF XY: 0.0733 AC XY: 53265 AN XY: 726996

African (AFR) AF: 0.0111 AC: 372 AN: 33478

American (AMR) AF: 0.0275 AC: 1230 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0361 AC: 942 AN: 26094

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39692

South Asian (SAS) AF: 0.00984 AC: 848 AN: 86208

European-Finnish (FIN) AF: 0.0966 AC: 5157 AN: 53384

Middle Eastern (MID) AF: 0.00902 AC: 52 AN: 5764

European-Non Finnish (NFE) AF: 0.0883 AC: 98158 AN: 1111780

Other (OTH) AF: 0.0659 AC: 3977 AN: 60370

GnomAD4 genome AF: 0.0541 AC: 8245 AN: 152286 Hom.: 338 Cov.: 33 AF XY: 0.0530 AC XY: 3943 AN XY: 74450

African (AFR) AF: 0.0159 AC: 661 AN: 41560

American (AMR) AF: 0.0395 AC: 605 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0354 AC: 123 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.00828 AC: 40 AN: 4832

European-Finnish (FIN) AF: 0.102 AC: 1081 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0819 AC: 5572 AN: 68002

Other (OTH) AF: 0.0572 AC: 121 AN: 2114

Alfa AF: 0.0683 Hom.: 229

Bravo AF: 0.0479

Asia WGS AF: 0.00924 AC: 33 AN: 3478

EpiCase AF: 0.0721

EpiControl AF: 0.0748

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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
BayesDel_noAF	Benign	-0.52
CADD	Benign	4.8
DANN	Benign	0.93
PhyloP100		3.3
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61751532; hg19: chr11-118769604; COSMIC: COSV52684911; COSMIC: COSV52684911;