chr1-231882143-G-A

Variant names:

• chr1-231882143-G-A
• rs10864698
• NM_018662.3:c.1981+63626G>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+63626G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,172 control chromosomes in the GnomAD database, including 1,143 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 0.11 (1143 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 5 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 = 0.303 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+63626G>A		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.2077+63626G>A		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.1981+63626G>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+63626G>A		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1981+63626G>A		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000535983.5	TSL:1	c.1981+63626G>A		intron	N/A	ENSP00000443996.1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17054 AN: 152054 Hom.: 1142 Cov.: 32

Gnomad AFR AF: 0.0806

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0835

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0738

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.112 AC: 17066 AN: 152172 Hom.: 1143 Cov.: 32 AF XY: 0.113 AC XY: 8371 AN XY: 74394

African (AFR) AF: 0.0805 AC: 3342 AN: 41518

American (AMR) AF: 0.141 AC: 2151 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0835 AC: 290 AN: 3472

East Asian (EAS) AF: 0.315 AC: 1626 AN: 5156

South Asian (SAS) AF: 0.162 AC: 781 AN: 4812

European-Finnish (FIN) AF: 0.0738 AC: 782 AN: 10594

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7767 AN: 68010

Other (OTH) AF: 0.120 AC: 254 AN: 2114

Alfa AF: 0.116 Hom.: 2179

Bravo AF: 0.118

Asia WGS AF: 0.234 AC: 816 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	6.2
DANN	Benign	0.48
PhyloP100		0.30
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: rs10864698; hg19: chr1-232017889;