rs3737597

Variant names:

• chr1-232037092-G-A
• rs3737597
• NM_018662.3:c.*261G>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.*261G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 277,472 control chromosomes in the GnomAD database, including 427 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 0.033 (152 hom., cov: 32)
  • Exomes 𝑓: 0.044 (275 hom.)
• Consequence: DISC1 NM_018662.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.*261G>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.*261G>A		3_prime_UTR_variant	Exon 13 of 13	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.*261G>A		3_prime_UTR_variant	Exon 13 of 13	5		ENSP00000355597.6
DISC1	ENST00000622252.4	c.*1367G>A		3_prime_UTR_variant	Exon 12 of 12	5		ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 5002 AN: 152002 Hom.: 151 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0576

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.0382

Gnomad FIN AF: 0.0189

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0276

Gnomad OTH AF: 0.0432

GnomAD4 exome AF: 0.0439 AC: 5500 AN: 125352 Hom.: 275 Cov.: 3 AF XY: 0.0424 AC XY: 2691 AN XY: 63536

Gnomad4 AFR exome AF: 0.0192 AC: 82 AN: 4266

Gnomad4 AMR exome AF: 0.0570 AC: 205 AN: 3594

Gnomad4 ASJ exome AF: 0.0557 AC: 277 AN: 4972

Gnomad4 EAS exome AF: 0.191 AC: 1995 AN: 10452

Gnomad4 SAS exome AF: 0.0338 AC: 44 AN: 1300

Gnomad4 FIN exome AF: 0.0230 AC: 208 AN: 9026

Gnomad4 NFE exome AF: 0.0281 AC: 2316 AN: 82478

Gnomad4 Remaining exome AF: 0.0411 AC: 353 AN: 8588

GnomAD4 genome AF: 0.0329 AC: 5010 AN: 152120 Hom.: 152 Cov.: 32 AF XY: 0.0331 AC XY: 2463 AN XY: 74358

Gnomad4 AFR AF: 0.0177 AC: 0.0176652 AN: 0.0176652

Gnomad4 AMR AF: 0.0576 AC: 0.057642 AN: 0.057642

Gnomad4 ASJ AF: 0.0513 AC: 0.0513264 AN: 0.0513264

Gnomad4 EAS AF: 0.156 AC: 0.156419 AN: 0.156419

Gnomad4 SAS AF: 0.0383 AC: 0.0382696 AN: 0.0382696

Gnomad4 FIN AF: 0.0189 AC: 0.0189036 AN: 0.0189036

Gnomad4 NFE AF: 0.0276 AC: 0.0275719 AN: 0.0275719

Gnomad4 OTH AF: 0.0433 AC: 0.043251 AN: 0.043251

Alfa AF: 0.0311 Hom.: 436

Bravo AF: 0.0355

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3737597; hg19: chr1-232172838;