11-57753377-A-G

Position:

• chr11-57753377-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000531074.1(ENSG00000254732):​n.*152+10393A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 985,002 control chromosomes in the GnomAD database, including 96,729 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 0.41 (13135 hom., cov: 33)
  • Exomes 𝑓: 0.45 (83594 hom.)
• Consequence: ENSG00000254732 ENST00000531074.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.868

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMX2-CTNND1	NR_037646.1	n.346+15709A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000254732	ENST00000531074.1	n.*152+10393A>G		intron_variant		3		ENSP00000457993.1
ENSG00000288534	ENST00000674060.1	n.103+15709A>G		intron_variant				ENSP00000501055.2

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61991 AN: 152030 Hom.: 13134 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.447 AC: 372279 AN: 832852 Hom.: 83594 Cov.: 31 AF XY: 0.448 AC XY: 172239 AN XY: 384628

Gnomad4 AFR exome AF: 0.429

Gnomad4 AMR exome AF: 0.342

Gnomad4 ASJ exome AF: 0.433

Gnomad4 EAS exome AF: 0.111

Gnomad4 SAS exome AF: 0.410

Gnomad4 FIN exome AF: 0.344

Gnomad4 NFE exome AF: 0.451

Gnomad4 OTH exome AF: 0.411

GnomAD4 genome AF: 0.408 AC: 62022 AN: 152150 Hom.: 13135 Cov.: 33 AF XY: 0.396 AC XY: 29453 AN XY: 74378

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.426

Alfa AF: 0.428 Hom.: 2260

Bravo AF: 0.412

Asia WGS AF: 0.217 AC: 757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.19
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs3017889; hg19: chr11-57520849;