NM_018662.3:c.67+12337G>A

Variant names:

• chr1-231639271-G-A
• rs823161
• NM_018662.3:c.67+12337G>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.67+12337G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,934 control chromosomes in the GnomAD database, including 11,655 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 0.38 (11655 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96
• Publications: 8 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 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.67+12337G>A		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.67+12337G>A		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.67+12337G>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.67+12337G>A		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.67+12337G>A		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000366633.7	TSL:1	c.67+12337G>A		intron	N/A	ENSP00000355593.3

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57803 AN: 151816 Hom.: 11636 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.381 AC: 57858 AN: 151934 Hom.: 11655 Cov.: 31 AF XY: 0.385 AC XY: 28614 AN XY: 74230

African (AFR) AF: 0.362 AC: 14978 AN: 41426

American (AMR) AF: 0.454 AC: 6932 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1341 AN: 3472

East Asian (EAS) AF: 0.807 AC: 4139 AN: 5130

South Asian (SAS) AF: 0.420 AC: 2024 AN: 4822

European-Finnish (FIN) AF: 0.374 AC: 3948 AN: 10544

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

European-Non Finnish (NFE) AF: 0.344 AC: 23400 AN: 67964

Other (OTH) AF: 0.379 AC: 798 AN: 2108

Alfa AF: 0.338 Hom.: 6355

Bravo AF: 0.389

Asia WGS AF: 0.558 AC: 1943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0050
DANN	Benign	0.70
PhyloP100		-3.0
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: rs823161; hg19: chr1-231775017;