1-231606829-T-C

Variant names:

• chr1-231606829-T-C
• rs4658879
• ENST00000602956.5:n.495+45574T>C

Variant summary

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

The ENST00000602956.5(TSNAX-DISC1):​n.495+45574T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,112 control chromosomes in the GnomAD database, including 41,301 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 0.73 (41301 hom., cov: 31)
• Consequence: TSNAX-DISC1 ENST00000602956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.854
• Publications: 7 publications found

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]

LINC00582 (HGNC:43842): (long intergenic non-protein coding RNA 582)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSNAX-DISC1	NR_028393.1	n.526-9815T>C		intron_variant	Intron 4 of 15
TSNAX-DISC1	NR_028394.1	n.654-9815T>C		intron_variant	Intron 5 of 13
TSNAX-DISC1	NR_028395.1	n.654-9815T>C		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+45574T>C		intron_variant	Intron 5 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111104 AN: 151992 Hom.: 41259 Cov.: 31

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.731 AC: 111198 AN: 152112 Hom.: 41301 Cov.: 31 AF XY: 0.728 AC XY: 54145 AN XY: 74344

African (AFR) AF: 0.633 AC: 26254 AN: 41486

American (AMR) AF: 0.642 AC: 9820 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2661 AN: 3468

East Asian (EAS) AF: 0.535 AC: 2758 AN: 5158

South Asian (SAS) AF: 0.833 AC: 4015 AN: 4820

European-Finnish (FIN) AF: 0.775 AC: 8199 AN: 10576

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54886 AN: 68006

Other (OTH) AF: 0.739 AC: 1555 AN: 2104

Alfa AF: 0.782 Hom.: 77870

Bravo AF: 0.714

Asia WGS AF: 0.721 AC: 2510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.65
PhyloP100		-0.85

Splicing

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

Other links and lift over

dbSNP: rs4658879; hg19: chr1-231742575;