chr1-231900399-A-G

Variant names:

• chr1-231900399-A-G
• rs860275
• NM_018662.3:c.1982-58429A>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.1982-58429A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 152,112 control chromosomes in the GnomAD database, including 6,099 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 0.25 (6099 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 4 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 (EAS) allele frequency at 95% confidence interval = 0.647 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.1982-58429A>G		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.2078-58429A>G		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.1982-58429A>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.1982-58429A>G		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1982-58429A>G		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000535983.5	TSL:1	c.1981+81882A>G		intron	N/A	ENSP00000443996.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38270 AN: 151994 Hom.: 6083 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.252 AC: 38332 AN: 152112 Hom.: 6099 Cov.: 32 AF XY: 0.258 AC XY: 19158 AN XY: 74358

African (AFR) AF: 0.377 AC: 15649 AN: 41466

American (AMR) AF: 0.278 AC: 4250 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 635 AN: 3472

East Asian (EAS) AF: 0.665 AC: 3427 AN: 5152

South Asian (SAS) AF: 0.345 AC: 1664 AN: 4828

European-Finnish (FIN) AF: 0.140 AC: 1480 AN: 10590

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10545 AN: 68002

Other (OTH) AF: 0.258 AC: 544 AN: 2110

Alfa AF: 0.193 Hom.: 4228

Bravo AF: 0.270

Asia WGS AF: 0.448 AC: 1556 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	1.3
DANN	Benign	0.29
PhyloP100		-0.28
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: rs860275; hg19: chr1-232036145;