rs61751532

chr11-118898895-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001378213.1(BCL9L):c.4020G>A(p.Gln1340=) 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, single submitter B:1
• Conservation: PhyloP100: 3.29

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

Verdict is Benign. Variant got -15 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_single_submitter, 1 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/exons	MANE	UniProt
BCL9L	NM_001378213.1	c.4020G>A	p.Gln1340=	synonymous_variant	10/10	ENST00000683865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL9L	ENST00000683865.1	c.4020G>A	p.Gln1340=	synonymous_variant	10/10		NM_001378213.1	P4
BCL9L	ENST00000334801.7	c.4020G>A	p.Gln1340=	synonymous_variant	8/8	1		P4
BCL9L	ENST00000526143.2	c.3909G>A	p.Gln1303=	synonymous_variant	8/8	5		A1

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

GnomAD3 exomes AF: 0.0535 AC: 13430 AN: 250948 Hom.: 554 AF XY: 0.0529 AC XY: 7175 AN XY: 135634

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 SAS exome AF: 0.00864

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

Gnomad4 AFR exome AF: 0.0111

Gnomad4 AMR exome AF: 0.0275

Gnomad4 ASJ exome AF: 0.0361

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00984

Gnomad4 FIN exome AF: 0.0966

Gnomad4 NFE exome AF: 0.0883

Gnomad4 OTH exome AF: 0.0659

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

Gnomad4 AFR AF: 0.0159

Gnomad4 AMR AF: 0.0395

Gnomad4 ASJ AF: 0.0354

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00828

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.0572

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:1

Revision: criteria provided, single submitter

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	4.8
Dann	Benign	0.93

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

Other links and lift over

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