rs3017889

Variant names:

• chr11-57753377-A-G
• rs3017889
• ENST00000531074.1:n.*152+10393A>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+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
• Publications: 5 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]

BTBD18 (HGNC:37214): (BTB domain containing 18) Predicted to be involved in several processes, including male gamete generation; piRNA biosynthetic process; and positive regulation of transcription elongation from RNA polymerase II promoter. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMX2-CTNND1	NR_037646.1	n.346+15709A>G		intron_variant	Intron 2 of 20
BTBD18	XM_017018128.2	c.-1296T>C		upstream_gene_variant			XP_016873617.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000254732	ENST00000531074.1	n.*152+10393A>G		intron_variant	Intron 2 of 3	3		ENSP00000457993.1
ENSG00000288534	ENST00000674060.2	n.250+15709A>G		intron_variant	Intron 2 of 19			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

African (AFR) AF: 0.429 AC: 6773 AN: 15780

American (AMR) AF: 0.342 AC: 337 AN: 986

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 2231 AN: 5150

East Asian (EAS) AF: 0.111 AC: 403 AN: 3634

South Asian (SAS) AF: 0.410 AC: 6748 AN: 16456

European-Finnish (FIN) AF: 0.344 AC: 99 AN: 288

Middle Eastern (MID) AF: 0.465 AC: 753 AN: 1620

European-Non Finnish (NFE) AF: 0.451 AC: 343705 AN: 761646

Other (OTH) AF: 0.411 AC: 11230 AN: 27292

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

African (AFR) AF: 0.432 AC: 17923 AN: 41522

American (AMR) AF: 0.362 AC: 5536 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1482 AN: 3472

East Asian (EAS) AF: 0.103 AC: 532 AN: 5150

South Asian (SAS) AF: 0.375 AC: 1808 AN: 4822

European-Finnish (FIN) AF: 0.309 AC: 3272 AN: 10598

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30125 AN: 67992

Other (OTH) AF: 0.426 AC: 900 AN: 2112

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
PhyloP100		-0.87
PromoterAI		0.070	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3017889; hg19: chr11-57520849;