chr1-231955186-C-T

Variant names:

• chr1-231955186-C-T
• rs821589
• NM_018662.3:c.1982-3642C>T

Variant summary

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

The NM_001164537.2(DISC1):​c.2078-3642C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,136 control chromosomes in the GnomAD database, including 5,852 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 0.21 (5852 hom., cov: 32)
• Consequence: DISC1 NM_001164537.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 7 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164537.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	NM_018662.3	MANE Select	c.1982-3642C>T		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.2078-3642C>T		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.1982-3642C>T		intron	N/A	NP_001012975.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000439617.8	TSL:5 MANE Select	c.1982-3642C>T		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1982-3642C>T		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000535983.5	TSL:1	c.1982-53599C>T		intron	N/A	ENSP00000443996.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32127 AN: 152018 Hom.: 5841 Cov.: 32

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0984

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0917

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.211 AC: 32174 AN: 152136 Hom.: 5852 Cov.: 32 AF XY: 0.207 AC XY: 15400 AN XY: 74398

African (AFR) AF: 0.492 AC: 20419 AN: 41470

American (AMR) AF: 0.116 AC: 1772 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3466

East Asian (EAS) AF: 0.193 AC: 997 AN: 5166

South Asian (SAS) AF: 0.116 AC: 558 AN: 4822

European-Finnish (FIN) AF: 0.0984 AC: 1042 AN: 10594

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.0917 AC: 6233 AN: 68008

Other (OTH) AF: 0.193 AC: 406 AN: 2108

Alfa AF: 0.137 Hom.: 3163

Bravo AF: 0.226

Asia WGS AF: 0.207 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.32
DANN	Benign	0.71
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs821589; hg19: chr1-232090932;