1-232022933-G-A

Variant names:

• chr1-232022933-G-A
• rs3524
• NM_018662.3:c.2308-3502G>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.2308-3502G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,928 control chromosomes in the GnomAD database, including 30,350 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 0.62 (30350 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 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.2308-3502G>A		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.2404-3502G>A		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.2242-3502G>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.2308-3502G>A		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.2242-3502G>A		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000622252.4	TSL:5	c.*849-3502G>A		intron	N/A	ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93440 AN: 151812 Hom.: 30307 Cov.: 31

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.616 AC: 93535 AN: 151928 Hom.: 30350 Cov.: 31 AF XY: 0.613 AC XY: 45533 AN XY: 74222

African (AFR) AF: 0.826 AC: 34230 AN: 41464

American (AMR) AF: 0.551 AC: 8403 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1914 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3570 AN: 5186

South Asian (SAS) AF: 0.561 AC: 2702 AN: 4816

European-Finnish (FIN) AF: 0.517 AC: 5433 AN: 10502

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35368 AN: 67932

Other (OTH) AF: 0.587 AC: 1236 AN: 2106

Alfa AF: 0.545 Hom.: 49208

Bravo AF: 0.631

Asia WGS AF: 0.629 AC: 2190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.71
PhyloP100		-0.20
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: rs3524; hg19: chr1-232158679;