chr11-118898733-A-C

Variant names:

• chr11-118898733-A-C
• NM_001378213.1:c.4182T>G
• BCL9L p.Pro1394Pro

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001378213.1(BCL9L):​c.4182T>G​(p.Pro1394Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P1394P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: BCL9L NM_001378213.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-1.65 with no splicing effect.

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.4182T>G	p.Pro1394Pro	synonymous	Exon 10 of 10	NP_001365142.1	Q86UU0-1
	BCL9L	NM_182557.4		c.4182T>G	p.Pro1394Pro	synonymous	Exon 8 of 8	NP_872363.1	Q86UU0-1
	BCL9L	NM_001378214.1		c.4071T>G	p.Pro1357Pro	synonymous	Exon 9 of 9	NP_001365143.1	A0A087WZX0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL9L	ENST00000683865.1	MANE Select	c.4182T>G	p.Pro1394Pro	synonymous	Exon 10 of 10	ENSP00000507778.1	Q86UU0-1
	BCL9L	ENST00000334801.7	TSL:1	c.4182T>G	p.Pro1394Pro	synonymous	Exon 8 of 8	ENSP00000335320.3	Q86UU0-1
	BCL9L	ENST00000913860.1		c.4182T>G	p.Pro1394Pro	synonymous	Exon 9 of 9	ENSP00000583919.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 81

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.8
DANN	Benign	0.61
PhyloP100		-1.6

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-118769442;