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GeneBe

11-118898550-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

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

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4.24 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1227 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BCL9LNM_001378213.1 linkuse as main transcriptc.4365G>A p.Pro1455= synonymous_variant 10/10 ENST00000683865.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BCL9LENST00000683865.1 linkuse as main transcriptc.4365G>A p.Pro1455= synonymous_variant 10/10 NM_001378213.1 P4Q86UU0-1
BCL9LENST00000334801.7 linkuse as main transcriptc.4365G>A p.Pro1455= synonymous_variant 8/81 P4Q86UU0-1
BCL9LENST00000526143.2 linkuse as main transcriptc.4254G>A p.Pro1418= synonymous_variant 8/85 A1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00806
AC:
1227
AN:
152144
Hom.:
15
Cov.:
32
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.:
3
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.:
19
Cov.:
35
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00811
AC:
1235
AN:
152262
Hom.:
15
Cov.:
32
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.:
7
Bravo
AF:
0.00942
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 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.

Other links and lift over

dbSNP: rs139914635; hg19: chr11-118769259; API