NM_018662.3:c.1982-59378G>A

Variant names:

• chr1-231899450-G-A
• rs821723
• NM_018662.3:c.1982-59378G>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.1982-59378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 152,212 control chromosomes in the GnomAD database, including 63,300 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 0.91 (63300 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1982-59378G>A		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.1982-59378G>A		intron_variant	Intron 9 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1982-59378G>A		intron_variant	Intron 9 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138586 AN: 152092 Hom.: 63254 Cov.: 31

Gnomad AFR AF: 0.953

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.890

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.871

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.883

Gnomad OTH AF: 0.915

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

GnomAD4 genome AF: 0.911 AC: 138691 AN: 152212 Hom.: 63300 Cov.: 31 AF XY: 0.911 AC XY: 67807 AN XY: 74396

African (AFR) AF: 0.953 AC: 39588 AN: 41538

American (AMR) AF: 0.932 AC: 14257 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 3089 AN: 3472

East Asian (EAS) AF: 0.990 AC: 5128 AN: 5182

South Asian (SAS) AF: 0.919 AC: 4427 AN: 4816

European-Finnish (FIN) AF: 0.871 AC: 9214 AN: 10582

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.883 AC: 60061 AN: 68008

Other (OTH) AF: 0.912 AC: 1926 AN: 2112

Alfa AF: 0.901 Hom.: 8812

Bravo AF: 0.915

Asia WGS AF: 0.928 AC: 3225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.78
PhyloP100		-0.039
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: rs821723; hg19: chr1-232035196;