1-231876203-G-A

Variant names:

• chr1-231876203-G-A
• rs1009587
• NM_018662.3:c.1981+57686G>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.1981+57686G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,934 control chromosomes in the GnomAD database, including 11,489 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 0.39 (11489 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 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.1981+57686G>A		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.2077+57686G>A		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.1981+57686G>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.1981+57686G>A		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1981+57686G>A		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000535983.5	TSL:1	c.1981+57686G>A		intron	N/A	ENSP00000443996.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58478 AN: 151816 Hom.: 11480 Cov.: 31

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.385 AC: 58516 AN: 151934 Hom.: 11489 Cov.: 31 AF XY: 0.388 AC XY: 28796 AN XY: 74238

African (AFR) AF: 0.332 AC: 13747 AN: 41392

American (AMR) AF: 0.401 AC: 6117 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1278 AN: 3470

East Asian (EAS) AF: 0.512 AC: 2636 AN: 5152

South Asian (SAS) AF: 0.415 AC: 1996 AN: 4814

European-Finnish (FIN) AF: 0.443 AC: 4679 AN: 10572

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26795 AN: 67950

Other (OTH) AF: 0.400 AC: 843 AN: 2110

Alfa AF: 0.391 Hom.: 1951

Bravo AF: 0.379

Asia WGS AF: 0.473 AC: 1643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.56
PhyloP100		-0.77
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: rs1009587; hg19: chr1-232011949; COSMIC: COSV64093589;