1-231744594-G-A

Variant names:

• chr1-231744594-G-A
• rs2793092
• NM_018662.3:c.1118-5332G>A

Variant summary

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

The NM_018662.3(DISC1):​c.1118-5332G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 151,960 control chromosomes in the GnomAD database, including 34,445 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 0.65 (34445 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.685
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018662.3. 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.1118-5332G>A		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.1118-810G>A		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.1118-5332G>A		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.1118-5332G>A		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1118-5332G>A		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000366633.7	TSL:1	c.1118-5332G>A		intron	N/A	ENSP00000355593.3

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99001 AN: 151842 Hom.: 34437 Cov.: 31

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.652 AC: 99015 AN: 151960 Hom.: 34445 Cov.: 31 AF XY: 0.653 AC XY: 48478 AN XY: 74278

African (AFR) AF: 0.391 AC: 16202 AN: 41412

American (AMR) AF: 0.672 AC: 10273 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2696 AN: 3466

East Asian (EAS) AF: 0.561 AC: 2891 AN: 5150

South Asian (SAS) AF: 0.742 AC: 3570 AN: 4814

European-Finnish (FIN) AF: 0.761 AC: 8029 AN: 10556

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53075 AN: 67972

Other (OTH) AF: 0.659 AC: 1390 AN: 2108

Alfa AF: 0.702 Hom.: 6610

Bravo AF: 0.627

Asia WGS AF: 0.596 AC: 2071 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.8
DANN	Benign	0.70
PhyloP100		0.69
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: rs2793092; hg19: chr1-231880340;