1-231763958-T-G

Variant names:

• chr1-231763958-T-G
• rs2793086
• NM_018662.3:c.1269-3182T>G

Variant summary

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

The NM_001164537.2(DISC1):​c.1365-3182T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,208 control chromosomes in the GnomAD database, including 2,014 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 0.15 (2014 hom., cov: 33)
• Consequence: DISC1 NM_001164537.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786
• Publications: 14 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 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.1269-3182T>G		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.1365-3182T>G		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.1269-3182T>G		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.1269-3182T>G		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1269-3182T>G		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000366633.7	TSL:1	c.1269-3182T>G		intron	N/A	ENSP00000355593.3

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23172 AN: 152092 Hom.: 2012 Cov.: 33

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0940

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.152 AC: 23177 AN: 152208 Hom.: 2014 Cov.: 33 AF XY: 0.147 AC XY: 10906 AN XY: 74390

African (AFR) AF: 0.0952 AC: 3955 AN: 41528

American (AMR) AF: 0.0938 AC: 1435 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 738 AN: 3468

East Asian (EAS) AF: 0.0252 AC: 131 AN: 5192

South Asian (SAS) AF: 0.122 AC: 586 AN: 4810

European-Finnish (FIN) AF: 0.188 AC: 1992 AN: 10594

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.203 AC: 13828 AN: 68008

Other (OTH) AF: 0.149 AC: 314 AN: 2112

Alfa AF: 0.183 Hom.: 11754

Bravo AF: 0.142

Asia WGS AF: 0.0720 AC: 257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.38
DANN	Benign	0.40
PhyloP100		-0.79
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: rs2793086; hg19: chr1-231899704;