rs61730467

Variant names:

• chr11-118901451-G-A
• rs61730467
• NM_001378213.1:c.2292C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-118901451-G-A
• chr11-118901451-G-T

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.2292C>T​(p.Pro764Pro) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.500
• Publications: 6 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=-0.78).
• BP6: Variant 11-118901451-G-A is Benign according to our data. Variant chr11-118901451-G-A is described in ClinVar as Benign. ClinVar VariationId is 402415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.5 with no splicing effect.
• BA1: 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 rank	MANE	Protein	UniProt
BCL9L	NM_001378213.1	c.2292C>T	p.Pro764Pro	synonymous_variant	Exon 8 of 10	ENST00000683865.1	NP_001365142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL9L	ENST00000683865.1	c.2292C>T	p.Pro764Pro	synonymous_variant	Exon 8 of 10		NM_001378213.1	ENSP00000507778.1
BCL9L	ENST00000334801.7	c.2292C>T	p.Pro764Pro	synonymous_variant	Exon 6 of 8	1		ENSP00000335320.3
BCL9L	ENST00000526143.2	c.2181C>T	p.Pro727Pro	synonymous_variant	Exon 6 of 8	5		ENSP00000482938.1
BCL9L	ENST00000530293.1	n.41-690C>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5698 AN: 152166 Hom.: 132 Cov.: 32

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

GnomAD2 exomes AF: 0.0374 AC: 9383 AN: 251032 AF XY: 0.0409

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 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

African (AFR) AF: 0.0564 AC: 1887 AN: 33480

American (AMR) AF: 0.0318 AC: 1423 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0553 AC: 1445 AN: 26134

East Asian (EAS) AF: 0.00159 AC: 63 AN: 39700

South Asian (SAS) AF: 0.0919 AC: 7923 AN: 86258

European-Finnish (FIN) AF: 0.0212 AC: 1132 AN: 53368

Middle Eastern (MID) AF: 0.0707 AC: 408 AN: 5768

European-Non Finnish (NFE) AF: 0.0266 AC: 29615 AN: 1111974

Other (OTH) AF: 0.0393 AC: 2371 AN: 60384

GnomAD4 genome AF: 0.0375 AC: 5704 AN: 152284 Hom.: 131 Cov.: 32 AF XY: 0.0378 AC XY: 2814 AN XY: 74462

African (AFR) AF: 0.0508 AC: 2110 AN: 41574

American (AMR) AF: 0.0425 AC: 651 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 190 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5168

South Asian (SAS) AF: 0.0912 AC: 440 AN: 4826

European-Finnish (FIN) AF: 0.0206 AC: 219 AN: 10620

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0285 AC: 1935 AN: 68006

Other (OTH) AF: 0.0586 AC: 124 AN: 2116

Alfa AF: 0.0308 Hom.: 148

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: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: MAF -

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	-0.78
CADD	Benign	2.8
DANN	Benign	0.85
PhyloP100		-0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs61730467; hg19: chr11-118772160; COSMIC: COSV52689779; COSMIC: COSV52689779;