1-231619133-G-C

Variant names:

• chr1-231619133-G-C
• rs6541280
• ENST00000602956.5:n.495+57878G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000602956.5(TSNAX-DISC1):​n.495+57878G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 152,148 control chromosomes in the GnomAD database, including 21,769 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 0.52 (21769 hom., cov: 33)
• Consequence: TSNAX-DISC1 ENST00000602956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65
• 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000602956.5. 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
	TSNAX-DISC1	NR_028393.1		n.788+2227G>C		intron	N/A
	TSNAX-DISC1	NR_028394.1		n.916+2227G>C		intron	N/A
	TSNAX-DISC1	NR_028395.1		n.916+2227G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSNAX-DISC1	ENST00000602956.5	TSL:2	n.495+57878G>C		intron	N/A	ENSP00000473532.1	C4P0D8
	TSNAX-DISC1	ENST00000602567.1	TSL:2	n.*197+2227G>C		intron	N/A	ENSP00000473456.1	C4P0D6
	TSNAX-DISC1	ENST00000602634.5	TSL:2	n.*213+2227G>C		intron	N/A	ENSP00000473307.1	C4P0D4

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79194 AN: 152030 Hom.: 21760 Cov.: 33

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.521 AC: 79224 AN: 152148 Hom.: 21769 Cov.: 33 AF XY: 0.517 AC XY: 38406 AN XY: 74358

African (AFR) AF: 0.393 AC: 16316 AN: 41508

American (AMR) AF: 0.496 AC: 7588 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2049 AN: 3470

East Asian (EAS) AF: 0.172 AC: 890 AN: 5180

South Asian (SAS) AF: 0.528 AC: 2543 AN: 4816

European-Finnish (FIN) AF: 0.584 AC: 6171 AN: 10574

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41676 AN: 67996

Other (OTH) AF: 0.546 AC: 1151 AN: 2108

Alfa AF: 0.435 Hom.: 1240

Bravo AF: 0.506

Asia WGS AF: 0.364 AC: 1264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		2.6

Splicing

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

Other links and lift over

dbSNP: rs6541280; hg19: chr1-231754879;