rs75656086

Positions:

• chr11-118902471-G-A

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.1272C>T​(p.Ser424=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,608,966 control chromosomes in the GnomAD database, including 416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (63 hom., cov: 33)
  • Exomes 𝑓: 0.012 (353 hom.)
• Consequence: BCL9L NM_001378213.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.87

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=-0.83).
• BP6: Variant 11-118902471-G-A is Benign according to our data. Variant chr11-118902471-G-A is described in ClinVar as [Benign]. Clinvar id is 402418.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.87 with no splicing effect.
• 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/exons	MANE	UniProt
BCL9L	NM_001378213.1	c.1272C>T	p.Ser424=	synonymous_variant	8/10	ENST00000683865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL9L	ENST00000683865.1	c.1272C>T	p.Ser424=	synonymous_variant	8/10		NM_001378213.1	P4
BCL9L	ENST00000334801.7	c.1272C>T	p.Ser424=	synonymous_variant	6/8	1		P4
BCL9L	ENST00000526143.2	c.1161C>T	p.Ser387=	synonymous_variant	6/8	5		A1
BCL9L	ENST00000530293.1	n.41-1710C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2491 AN: 152214 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.0152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00726

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0165

Gnomad FIN AF: 0.0490

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00763

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.0204 AC: 4940 AN: 242632 Hom.: 205 AF XY: 0.0198 AC XY: 2617 AN XY: 132380

Gnomad AFR exome AF: 0.0168

Gnomad AMR exome AF: 0.00385

Gnomad ASJ exome AF: 0.00473

Gnomad EAS exome AF: 0.128

Gnomad SAS exome AF: 0.0162

Gnomad FIN exome AF: 0.0433

Gnomad NFE exome AF: 0.00685

Gnomad OTH exome AF: 0.0133

GnomAD4 exome AF: 0.0117 AC: 17022 AN: 1456634 Hom.: 353 Cov.: 41 AF XY: 0.0119 AC XY: 8603 AN XY: 724606

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.00429

Gnomad4 ASJ exome AF: 0.00347

Gnomad4 EAS exome AF: 0.0905

Gnomad4 SAS exome AF: 0.0164

Gnomad4 FIN exome AF: 0.0411

Gnomad4 NFE exome AF: 0.00737

Gnomad4 OTH exome AF: 0.0161

GnomAD4 genome AF: 0.0164 AC: 2497 AN: 152332 Hom.: 63 Cov.: 33 AF XY: 0.0185 AC XY: 1376 AN XY: 74484

Gnomad4 AFR AF: 0.0154

Gnomad4 AMR AF: 0.00725

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0166

Gnomad4 FIN AF: 0.0490

Gnomad4 NFE AF: 0.00763

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.00800 Hom.: 5

Bravo AF: 0.0136

Asia WGS AF: 0.0530 AC: 185 AN: 3478

EpiCase AF: 0.00600

EpiControl AF: 0.00617

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	-0.83
CADD	Benign	0.12
DANN	Benign	0.90
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

Other links and lift over

dbSNP: rs75656086; hg19: chr11-118773180;