rs2738880

Variant names:

• chr1-231818153-A-G
• rs2738880
• NM_018662.3:c.1793-176A>G

Variant summary

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

The NM_018662.3(DISC1):​c.1793-176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.094 in 152,234 control chromosomes in the GnomAD database, including 973 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 0.094 (973 hom., cov: 33)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.95
• Publications: 7 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]

ENSG00000286071 (HGNC:):

DISC2 (HGNC:2889): (disrupted in schizophrenia 2) DISC2 is thought to specify a noncoding RNA molecule antisense to DISC1 (MIM 605210). Both genes were found to be disrupted by a translocation in a large schizophrenia (MIM 181500) kindred.[supplied by OMIM, Jul 2002]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1793-176A>G		intron_variant	Intron 8 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1793-176A>G		intron_variant	Intron 8 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1793-176A>G		intron_variant	Intron 8 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.*1654-176A>G		intron_variant	Intron 12 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.0939 AC: 14282 AN: 152116 Hom.: 969 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0427

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0528

Gnomad OTH AF: 0.0918

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

GnomAD4 genome AF: 0.0940 AC: 14306 AN: 152234 Hom.: 973 Cov.: 33 AF XY: 0.0955 AC XY: 7109 AN XY: 74426

African (AFR) AF: 0.130 AC: 5402 AN: 41522

American (AMR) AF: 0.115 AC: 1759 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 370 AN: 3468

East Asian (EAS) AF: 0.353 AC: 1825 AN: 5172

South Asian (SAS) AF: 0.133 AC: 641 AN: 4830

European-Finnish (FIN) AF: 0.0427 AC: 453 AN: 10614

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0528 AC: 3591 AN: 68012

Other (OTH) AF: 0.0941 AC: 199 AN: 2114

Alfa AF: 0.0722 Hom.: 940

Bravo AF: 0.102

Asia WGS AF: 0.234 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.6
DANN	Benign	0.56
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2738880; hg19: chr1-231953899;