rs78780803

chr11-118902116-T-Cchr11-118902116-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (86 hom., cov: 32)
  • Exomes 𝑓: 0.013 (381 hom.)
• Consequence: BCL9L NM_001378213.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.92

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 -14 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 id is 402417.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
BCL9L	NM_001378213.1	c.1627A>G	p.Ser543Gly	missense_variant	8/10	ENST00000683865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL9L	ENST00000683865.1	c.1627A>G	p.Ser543Gly	missense_variant	8/10		NM_001378213.1	P4
BCL9L	ENST00000334801.7	c.1627A>G	p.Ser543Gly	missense_variant	6/8	1		P4
BCL9L	ENST00000526143.2	c.1516A>G	p.Ser506Gly	missense_variant	6/8	5		A1
BCL9L	ENST00000530293.1	n.41-1355A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0224 AC: 3403 AN: 151966 Hom.: 86 Cov.: 32

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

GnomAD3 exomes AF: 0.0218 AC: 5470 AN: 251150 Hom.: 218 AF XY: 0.0208 AC XY: 2823 AN XY: 135780

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 SAS exome AF: 0.0162

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.: 36 AF XY: 0.0126 AC XY: 9134 AN XY: 727206

Gnomad4 AFR exome AF: 0.0355

Gnomad4 AMR exome AF: 0.00461

Gnomad4 ASJ exome AF: 0.00352

Gnomad4 EAS exome AF: 0.0910

Gnomad4 SAS exome AF: 0.0163

Gnomad4 FIN exome AF: 0.0422

Gnomad4 NFE exome AF: 0.00758

Gnomad4 OTH exome AF: 0.0174

GnomAD4 genome AF: 0.0224 AC: 3413 AN: 152086 Hom.: 86 Cov.: 32 AF XY: 0.0242 AC XY: 1797 AN XY: 74348

Gnomad4 AFR AF: 0.0366

Gnomad4 AMR AF: 0.00856

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0166

Gnomad4 FIN AF: 0.0495

Gnomad4 NFE AF: 0.00777

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.0118 Hom.: 64

Bravo AF: 0.0206

TwinsUK AF: 0.00647 AC: 24

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.0370 AC: 163

ESP6500EA AF: 0.00733 AC: 63

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: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
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	18
Dann	Benign	0.83
DEOGEN2	Benign	0.082	T;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.25	T;T
MetaRNN	Benign	0.0011	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N;.
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.54	T
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	T
GERP RS		4.6
Varity_R		0.030
gMVP		0.12

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: rs78780803; hg19: chr11-118772825; COSMIC: COSV52689277; COSMIC: COSV52689277;