rs1754603

Variant names:

• chr1-232002876-C-T
• rs1754603
• NM_018662.3:c.2043-5909C>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.2043-5909C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,790 control chromosomes in the GnomAD database, including 6,430 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 0.29 (6430 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.2043-5909C>T		intron_variant	Intron 10 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.2043-5909C>T		intron_variant	Intron 10 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.2043-5909C>T		intron_variant	Intron 10 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43246 AN: 151670 Hom.: 6421 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.285 AC: 43288 AN: 151790 Hom.: 6430 Cov.: 32 AF XY: 0.284 AC XY: 21061 AN XY: 74182

African (AFR) AF: 0.333 AC: 13769 AN: 41378

American (AMR) AF: 0.181 AC: 2766 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 854 AN: 3464

East Asian (EAS) AF: 0.119 AC: 616 AN: 5156

South Asian (SAS) AF: 0.274 AC: 1321 AN: 4818

European-Finnish (FIN) AF: 0.329 AC: 3458 AN: 10518

Middle Eastern (MID) AF: 0.224 AC: 65 AN: 290

European-Non Finnish (NFE) AF: 0.287 AC: 19487 AN: 67912

Other (OTH) AF: 0.259 AC: 545 AN: 2106

Alfa AF: 0.285 Hom.: 772

Bravo AF: 0.272

Asia WGS AF: 0.220 AC: 764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.65
DANN	Benign	0.27
PhyloP100		-0.59
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: rs1754603; hg19: chr1-232138622; COSMIC: COSV64093789;