11-57758411-A-G

Variant names:

• chr11-57758411-A-G
• rs501738
• ENST00000531074.1:n.*152+15427A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000531074.1(ENSG00000254732):​n.*152+15427A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,138 control chromosomes in the GnomAD database, including 7,127 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (7127 hom., cov: 33)
• Consequence: ENSG00000254732 ENST00000531074.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 2 publications found

Genes affected

ENSG00000254732 (HGNC:):

CTNND1 (HGNC:2515): (catenin delta 1) This gene encodes a member of the Armadillo protein family, which function in adhesion between cells and signal transduction. Multiple translation initiation codons and alternative splicing result in many different isoforms being translated. Not all of the full-length natures of the described transcript variants have been determined. Read-through transcription also exists between this gene and the neighboring upstream thioredoxin-related transmembrane protein 2 (TMX2) gene. [provided by RefSeq, Dec 2010]

TMX2-CTNND1 (HGNC:41992): (TMX2-CTNND1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring TMX2 (thioredoxin-related transmembrane protein 2) and CTNND1 (catenin, cadherin-associated protein, delta 1) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000531074.1. 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
	TMX2-CTNND1	NR_037646.1		n.346+20743A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000254732	ENST00000531074.1	TSL:3	n.*152+15427A>G		intron	N/A	ENSP00000457993.1	H3BV83
	ENSG00000288534	ENST00000674060.2		n.250+20743A>G		intron	N/A	ENSP00000501055.2	A0A669KBH8
	CTNND1	ENST00000529919.5	TSL:5	c.-214+5004A>G		intron	N/A	ENSP00000434808.1	C9JZR2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43017 AN: 152020 Hom.: 7114 Cov.: 33

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.276

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.283 AC: 43040 AN: 152138 Hom.: 7127 Cov.: 33 AF XY: 0.296 AC XY: 22000 AN XY: 74358

African (AFR) AF: 0.225 AC: 9324 AN: 41510

American (AMR) AF: 0.412 AC: 6299 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 939 AN: 3472

East Asian (EAS) AF: 0.786 AC: 4070 AN: 5180

South Asian (SAS) AF: 0.346 AC: 1672 AN: 4826

European-Finnish (FIN) AF: 0.333 AC: 3510 AN: 10546

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.239 AC: 16269 AN: 68004

Other (OTH) AF: 0.280 AC: 591 AN: 2110

Alfa AF: 0.149 Hom.: 269

Bravo AF: 0.293

Asia WGS AF: 0.575 AC: 2002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.64
PhyloP100		-1.5
Mutation Taster		=100/0	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

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

Other links and lift over

dbSNP: rs501738; hg19: chr11-57525883;