rs1025526

Variant names:

• chr1-231614895-C-T
• rs1025526
• ENST00000602956.5:n.495+53640C>T

Variant summary

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

The ENST00000602956.5(TSNAX-DISC1):​n.495+53640C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,120 control chromosomes in the GnomAD database, including 24,208 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 0.54 (24208 hom., cov: 33)
• Consequence: TSNAX-DISC1 ENST00000602956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.462

Genes affected

TSNAX-DISC1 (HGNC:49177): (TSNAX-DISC1 readthrough (NMD candidate)) This gene represents naturally occurring read-through transcription between the neighboring TSNAX (translin-associated factor X) and DISC1 (disrupted in schizophrenia 1) genes on chromosome 1. Alternative splicing results in multiple transcript variants, all of which are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to be protein-coding. These alterations in gene processing may be associated with risk for psychiatric illness, most notably, schizophrenia. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSNAX-DISC1	NR_028393.1	n.526-1749C>T		intron_variant	Intron 4 of 15
TSNAX-DISC1	NR_028394.1	n.654-1749C>T		intron_variant	Intron 5 of 13
TSNAX-DISC1	NR_028395.1	n.654-1749C>T		intron_variant	Intron 5 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSNAX-DISC1	ENST00000602956.5	n.495+53640C>T		intron_variant	Intron 5 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82749 AN: 152002 Hom.: 24199 Cov.: 33

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.544 AC: 82777 AN: 152120 Hom.: 24208 Cov.: 33 AF XY: 0.540 AC XY: 40130 AN XY: 74352

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.576

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.584

Alfa AF: 0.600 Hom.: 3517

Bravo AF: 0.525

Asia WGS AF: 0.413 AC: 1433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1025526; hg19: chr1-231750641; COSMIC: COSV71449416;