rs1538975

Variant names:

• chr1-231692626-C-T
• rs1538975
• NM_018662.3:c.68-1200C>T

Variant summary

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

The NM_018662.3(DISC1):​c.68-1200C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,126 control chromosomes in the GnomAD database, including 6,038 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 0.28 (6038 hom., cov: 33)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 3 publications found

Genes affected

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]

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.68-1200C>T		intron_variant	Intron 1 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.68-1200C>T		intron_variant	Intron 1 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.68-1200C>T		intron_variant	Intron 1 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.496-1200C>T		intron_variant	Intron 5 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41900 AN: 152008 Hom.: 6035 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.276 AC: 41935 AN: 152126 Hom.: 6038 Cov.: 33 AF XY: 0.272 AC XY: 20229 AN XY: 74348

African (AFR) AF: 0.195 AC: 8089 AN: 41494

American (AMR) AF: 0.319 AC: 4880 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1001 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1256 AN: 5152

South Asian (SAS) AF: 0.240 AC: 1157 AN: 4828

European-Finnish (FIN) AF: 0.282 AC: 2982 AN: 10586

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21665 AN: 67986

Other (OTH) AF: 0.315 AC: 666 AN: 2116

Alfa AF: 0.290 Hom.: 1071

Bravo AF: 0.276

Asia WGS AF: 0.238 AC: 832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.025
DANN	Benign	0.31
PhyloP100		-1.6
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: rs1538975; hg19: chr1-231828372;