NM_018662.3:c.1118-21670G>T

Variant names:

• chr1-231728256-G-T
• rs2812385
• NM_018662.3:c.1118-21670G>T

Variant summary

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

The NM_018662.3(DISC1):​c.1118-21670G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,024 control chromosomes in the GnomAD database, including 26,327 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 0.58 (26327 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.793
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1118-21670G>T		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.1118-21670G>T		intron_variant	Intron 3 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1118-21670G>T		intron_variant	Intron 3 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.*979-21670G>T		intron_variant	Intron 7 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88471 AN: 151906 Hom.: 26318 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.582 AC: 88502 AN: 152024 Hom.: 26327 Cov.: 32 AF XY: 0.583 AC XY: 43303 AN XY: 74316

African (AFR) AF: 0.449 AC: 18630 AN: 41452

American (AMR) AF: 0.608 AC: 9288 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2371 AN: 3470

East Asian (EAS) AF: 0.579 AC: 2987 AN: 5158

South Asian (SAS) AF: 0.679 AC: 3275 AN: 4822

European-Finnish (FIN) AF: 0.584 AC: 6171 AN: 10566

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43739 AN: 67958

Other (OTH) AF: 0.585 AC: 1235 AN: 2110

Alfa AF: 0.625 Hom.: 80515

Bravo AF: 0.574

Asia WGS AF: 0.578 AC: 2007 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.52
PhyloP100		0.79
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: rs2812385; hg19: chr1-231864002;