NM_001378213.1:c.4405A>C

Variant names:

• chr11-118898510-T-G
• NM_001378213.1:c.4405A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378213.1(BCL9L):​c.4405A>C​(p.Met1469Leu) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BCL9L NM_001378213.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.79
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2341047).

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.4405A>C	p.Met1469Leu	missense	Exon 10 of 10	NP_001365142.1	Q86UU0-1
	BCL9L	NM_182557.4		c.4405A>C	p.Met1469Leu	missense	Exon 8 of 8	NP_872363.1	Q86UU0-1
	BCL9L	NM_001378214.1		c.4294A>C	p.Met1432Leu	missense	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.4405A>C	p.Met1469Leu	missense	Exon 10 of 10	ENSP00000507778.1	Q86UU0-1
	BCL9L	ENST00000334801.7	TSL:1	c.4405A>C	p.Met1469Leu	missense	Exon 8 of 8	ENSP00000335320.3	Q86UU0-1
	BCL9L	ENST00000913860.1		c.4405A>C	p.Met1469Leu	missense	Exon 9 of 9	ENSP00000583919.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1449214 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 718652

African (AFR) AF: 0.00 AC: 0 AN: 33258

American (AMR) AF: 0.00 AC: 0 AN: 44116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25822

East Asian (EAS) AF: 0.00 AC: 0 AN: 39336

South Asian (SAS) AF: 0.00 AC: 0 AN: 85788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103290

Other (OTH) AF: 0.00 AC: 0 AN: 59722

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	0.0046	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Benign	0.92
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.098
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.8
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.28
Sift	Benign	0.084	T
Sift4G	Benign	0.33	T
Polyphen		0.0030	B
Vest4		0.48
MutPred		0.27		Loss of catalytic residue at M1469 (P = 0.0325)
MVP		0.70
MPC		0.19
ClinPred		0.51	D
GERP RS		3.7
Varity_R		0.37
gMVP		0.17
Mutation Taster		=97/3	polymorphism

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

hg19: chr11-118769219;