rs1340982

Variant names:

• chr1-231726286-G-A
• rs1340982
• NM_018662.3:c.1118-23640G>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.1118-23640G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,116 control chromosomes in the GnomAD database, including 11,732 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 (11732 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1118-23640G>A		intron_variant	Intron 3 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1118-23640G>A		intron_variant	Intron 3 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1118-23640G>A		intron_variant	Intron 3 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.*979-23640G>A		intron_variant	Intron 7 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58594 AN: 151998 Hom.: 11711 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.386 AC: 58658 AN: 152116 Hom.: 11732 Cov.: 32 AF XY: 0.379 AC XY: 28203 AN XY: 74344

African (AFR) AF: 0.493 AC: 20438 AN: 41486

American (AMR) AF: 0.358 AC: 5467 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1164 AN: 3468

East Asian (EAS) AF: 0.406 AC: 2091 AN: 5148

South Asian (SAS) AF: 0.284 AC: 1367 AN: 4820

European-Finnish (FIN) AF: 0.320 AC: 3392 AN: 10594

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23545 AN: 68000

Other (OTH) AF: 0.409 AC: 862 AN: 2110

Alfa AF: 0.363 Hom.: 1290

Bravo AF: 0.398

Asia WGS AF: 0.366 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.43
DANN	Benign	0.35
PhyloP100		-0.041
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1340982; hg19: chr1-231862032;