1-231942868-T-C

Variant names:

• chr1-231942868-T-C
• rs4658966
• NM_018662.3:c.1982-15960T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018662.3(DISC1):​c.1982-15960T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,108 control chromosomes in the GnomAD database, including 3,701 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 0.19 (3701 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.984
• Publications: 12 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]

DISC1-IT1 (HGNC:41325): (DISC1 intronic transcript 1)

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1982-15960T>C		intron_variant	Intron 9 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1982-15960T>C		intron_variant	Intron 9 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1982-15960T>C		intron_variant	Intron 9 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29443 AN: 151990 Hom.: 3697 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.194 AC: 29463 AN: 152108 Hom.: 3701 Cov.: 32 AF XY: 0.200 AC XY: 14907 AN XY: 74354

African (AFR) AF: 0.164 AC: 6802 AN: 41518

American (AMR) AF: 0.277 AC: 4233 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 807 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3535 AN: 5140

South Asian (SAS) AF: 0.262 AC: 1263 AN: 4822

European-Finnish (FIN) AF: 0.162 AC: 1717 AN: 10576

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10466 AN: 67992

Other (OTH) AF: 0.221 AC: 467 AN: 2114

Alfa AF: 0.175 Hom.: 12049

Bravo AF: 0.203

Asia WGS AF: 0.432 AC: 1501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.46
PhyloP100		-0.98
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: rs4658966; hg19: chr1-232078614;