1-231632793-A-G

Variant names:

• chr1-231632793-A-G
• rs751229
• NM_018662.3:c.67+5859A>G

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+5859A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,020 control chromosomes in the GnomAD database, including 16,612 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 0.46 (16612 hom., cov: 33)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 20 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 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+5859A>G		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.67+5859A>G		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.67+5859A>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.67+5859A>G		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.67+5859A>G		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000366633.7	TSL:1	c.67+5859A>G		intron	N/A	ENSP00000355593.3

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69520 AN: 151902 Hom.: 16577 Cov.: 33

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.458 AC: 69608 AN: 152020 Hom.: 16612 Cov.: 33 AF XY: 0.461 AC XY: 34275 AN XY: 74324

African (AFR) AF: 0.518 AC: 21472 AN: 41420

American (AMR) AF: 0.495 AC: 7551 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1479 AN: 3462

East Asian (EAS) AF: 0.823 AC: 4269 AN: 5184

South Asian (SAS) AF: 0.468 AC: 2255 AN: 4822

European-Finnish (FIN) AF: 0.413 AC: 4363 AN: 10556

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.396 AC: 26900 AN: 67998

Other (OTH) AF: 0.449 AC: 948 AN: 2110

Alfa AF: 0.392 Hom.: 11397

Bravo AF: 0.469

Asia WGS AF: 0.618 AC: 2150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.65
DANN	Benign	0.47
PhyloP100		-2.0
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: rs751229; hg19: chr1-231768539;