Variant 11-118898550-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001378213.1(BCL9L):c.4365G>A(p.Pro1455=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,605,508 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 15 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 19 hom. )

Consequence

BCL9L
NM_001378213.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.24

Variant links:

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]

BCL9L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 11-118898550-C-T is Benign according to our data. Variant chr11-118898550-C-T is described in ClinVar as [Benign]. Clinvar id is 779376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.24 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00811 (1235/152262) while in subpopulation AFR AF= 0.0284 (1182/41566). AF 95% confidence interval is 0.0271. There are 15 homozygotes in gnomad4. There are 561 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1235 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL9L	NM_001378213.1 linkuse as main transcript	c.4365G>A	p.Pro1455=	synonymous_variant	10/10	ENST00000683865.1	NP_001365142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL9L	ENST00000683865.1 linkuse as main transcript	c.4365G>A	p.Pro1455=	synonymous_variant	10/10		NM_001378213.1	ENSP00000507778	P4	Q86UU0-1
BCL9L	ENST00000334801.7 linkuse as main transcript	c.4365G>A	p.Pro1455=	synonymous_variant	8/8	1		ENSP00000335320	P4	Q86UU0-1
BCL9L	ENST00000526143.2 linkuse as main transcript	c.4254G>A	p.Pro1418=	synonymous_variant	8/8	5		ENSP00000482938	A1

Frequencies

GnomAD3 genomes

AF:

0.00806

AC:

1227

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0283

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00208

AC:

496

AN:

238938

Hom.:

AF XY:

0.00153

AC XY:

200

AN XY:

130810

show subpopulations

Gnomad AFR exome

AF:

0.0284

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.000570

Gnomad NFE exome

AF:

0.000122

Gnomad OTH exome

AF:

0.000861

GnomAD4 exome

AF:

0.000875

AC:

1272

AN:

1453246

Hom.:

Cov.:

AF XY:

0.000708

AC XY:

511

AN XY:

721930

show subpopulations

Gnomad4 AFR exome

AF:

0.0279

Gnomad4 AMR exome

AF:

0.00138

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000818

Gnomad4 FIN exome

AF:

0.000577

Gnomad4 NFE exome

AF:

0.000117

Gnomad4 OTH exome

AF:

0.00165

GnomAD4 genome

AF:

0.00811

AC:

1235

AN:

152262

Hom.:

Cov.:

AF XY:

0.00753

AC XY:

561

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0284

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00420

Hom.:

Bravo

AF:

0.00942

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.11

DANN

Benign

0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over