1-231818681-C-T

Variant names:

• chr1-231818681-C-T
• rs1535530
• ENST00000602956.5:n.*2006C>T

Variant summary

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

The ENST00000602956.5(TSNAX-DISC1):​n.*2006C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 1,437,096 control chromosomes in the GnomAD database, including 334,882 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 0.66 (33419 hom., cov: 33)
  • Exomes 𝑓: 0.68 (301463 hom.)
• Consequence: TSNAX-DISC1 ENST00000602956.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• Publications: 10 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]

DISC1 (HGNC:2888): (DISC1 scaffold protein) This gene encodes a protein with multiple coiled coil motifs which is located in the nucleus, cytoplasm and mitochondria. The protein is involved in neurite outgrowth and cortical development through its interaction with other proteins. This gene is disrupted in a t(1;11)(q42.1;q14.3) translocation which segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ENSG00000286071 (HGNC:):

DISC2 (HGNC:2889): (disrupted in schizophrenia 2) DISC2 is thought to specify a noncoding RNA molecule antisense to DISC1 (MIM 605210). Both genes were found to be disrupted by a translocation in a large schizophrenia (MIM 181500) kindred.[supplied by OMIM, Jul 2002]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1981+164C>T		intron_variant	Intron 9 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSNAX-DISC1	ENST00000602956.5	n.*2006C>T		non_coding_transcript_exon_variant	Exon 13 of 13	2		ENSP00000473532.1
TSNAX-DISC1	ENST00000602956.5	n.*2006C>T		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000473532.1
DISC1	ENST00000439617.8	c.1981+164C>T		intron_variant	Intron 9 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1981+164C>T		intron_variant	Intron 9 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100209 AN: 151876 Hom.: 33396 Cov.: 33

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.673

GnomAD4 exome AF: 0.684 AC: 879237 AN: 1285102 Hom.: 301463 Cov.: 41 AF XY: 0.684 AC XY: 426146 AN XY: 622704

African (AFR) AF: 0.567 AC: 16002 AN: 28220

American (AMR) AF: 0.763 AC: 15119 AN: 19806

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 12805 AN: 18940

East Asian (EAS) AF: 0.780 AC: 27051 AN: 34688

South Asian (SAS) AF: 0.676 AC: 40743 AN: 60256

European-Finnish (FIN) AF: 0.710 AC: 24064 AN: 33912

Middle Eastern (MID) AF: 0.613 AC: 3096 AN: 5048

European-Non Finnish (NFE) AF: 0.683 AC: 704150 AN: 1030766

Other (OTH) AF: 0.677 AC: 36207 AN: 53466

GnomAD4 genome AF: 0.660 AC: 100279 AN: 151994 Hom.: 33419 Cov.: 33 AF XY: 0.664 AC XY: 49307 AN XY: 74298

African (AFR) AF: 0.569 AC: 23576 AN: 41408

American (AMR) AF: 0.729 AC: 11139 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2290 AN: 3468

East Asian (EAS) AF: 0.781 AC: 4030 AN: 5158

South Asian (SAS) AF: 0.683 AC: 3293 AN: 4818

European-Finnish (FIN) AF: 0.698 AC: 7373 AN: 10556

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46449 AN: 67984

Other (OTH) AF: 0.676 AC: 1426 AN: 2110

Alfa AF: 0.670 Hom.: 92697

Bravo AF: 0.657

Asia WGS AF: 0.723 AC: 2513 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	6.8
DANN	Benign	0.77
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1535530; hg19: chr1-231954427;