11-118901038-A-G

Variant names:

• chr11-118901038-A-G
• rs34123504
• NM_001378213.1:c.2705T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378213.1(BCL9L):​c.2705T>C​(p.Val902Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,577,720 control chromosomes in the GnomAD database, including 391 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (53 hom., cov: 32)
  • Exomes 𝑓: 0.011 (338 hom.)
• Consequence: BCL9L NM_001378213.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.38
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002446711).
• BP6: Variant 11-118901038-A-G is Benign according to our data. Variant chr11-118901038-A-G is described in ClinVar as Benign. ClinVar VariationId is 402414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378213.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL9L	NM_001378213.1	MANE Select	c.2705T>C	p.Val902Ala	missense	Exon 8 of 10	NP_001365142.1
	BCL9L	NM_182557.4		c.2705T>C	p.Val902Ala	missense	Exon 6 of 8	NP_872363.1
	BCL9L	NM_001378214.1		c.2594T>C	p.Val865Ala	missense	Exon 7 of 9	NP_001365143.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL9L	ENST00000683865.1	MANE Select	c.2705T>C	p.Val902Ala	missense	Exon 8 of 10	ENSP00000507778.1
	BCL9L	ENST00000334801.7	TSL:1	c.2705T>C	p.Val902Ala	missense	Exon 6 of 8	ENSP00000335320.3
	BCL9L	ENST00000913860.1		c.2705T>C	p.Val902Ala	missense	Exon 7 of 9	ENSP00000583919.1

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1929 AN: 152088 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0165

Gnomad FIN AF: 0.0492

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00760

Gnomad OTH AF: 0.00862

GnomAD2 exomes AF: 0.0199 AC: 4465 AN: 224230 AF XY: 0.0198

Gnomad AFR exome AF: 0.00294

Gnomad AMR exome AF: 0.00227

Gnomad ASJ exome AF: 0.00514

Gnomad EAS exome AF: 0.128

Gnomad FIN exome AF: 0.0434

Gnomad NFE exome AF: 0.00690

Gnomad OTH exome AF: 0.0125

GnomAD4 exome AF: 0.0114 AC: 16292 AN: 1425514 Hom.: 338 Cov.: 35 AF XY: 0.0116 AC XY: 8210 AN XY: 704850

African (AFR) AF: 0.00135 AC: 44 AN: 32556

American (AMR) AF: 0.00280 AC: 114 AN: 40774

Ashkenazi Jewish (ASJ) AF: 0.00350 AC: 82 AN: 23432

East Asian (EAS) AF: 0.0908 AC: 3571 AN: 39320

South Asian (SAS) AF: 0.0163 AC: 1306 AN: 80054

European-Finnish (FIN) AF: 0.0416 AC: 2164 AN: 52034

Middle Eastern (MID) AF: 0.00324 AC: 18 AN: 5554

European-Non Finnish (NFE) AF: 0.00744 AC: 8128 AN: 1093074

Other (OTH) AF: 0.0147 AC: 865 AN: 58716

GnomAD4 genome AF: 0.0127 AC: 1926 AN: 152206 Hom.: 53 Cov.: 32 AF XY: 0.0149 AC XY: 1109 AN XY: 74402

African (AFR) AF: 0.00221 AC: 92 AN: 41536

American (AMR) AF: 0.00608 AC: 93 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3470

East Asian (EAS) AF: 0.113 AC: 584 AN: 5166

South Asian (SAS) AF: 0.0166 AC: 80 AN: 4832

European-Finnish (FIN) AF: 0.0492 AC: 522 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00761 AC: 517 AN: 67978

Other (OTH) AF: 0.00853 AC: 18 AN: 2110

Alfa AF: 0.0104 Hom.: 88

Bravo AF: 0.00936

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.00432 AC: 19

ESP6500EA AF: 0.00722 AC: 62

ExAC AF: 0.0174 AC: 2106

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Benign	0.84
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.4
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.044
Sift	Benign	0.76	T
Sift4G	Benign	0.78	T
Polyphen		0.040	B
Vest4		0.15
MPC		0.25
ClinPred		0.0047	T
GERP RS		4.5
Varity_R		0.036
gMVP		0.26
Mutation Taster		=98/2	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: rs34123504; hg19: chr11-118771747; COSMIC: COSV107344544; COSMIC: COSV107344544;