rs3082

Variant names:

• chr1-231866646-A-G
• rs3082
• ENST00000366636.8:c.*68A>G

Variant summary

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

The ENST00000366636.8(DISC1):​c.*68A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,552,548 control chromosomes in the GnomAD database, including 99,204 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 0.33 (8475 hom., cov: 32)
  • Exomes 𝑓: 0.36 (90729 hom.)
• Consequence: DISC1 ENST00000366636.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 18 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1981+48129A>G		intron_variant	Intron 9 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1981+48129A>G		intron_variant	Intron 9 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1981+48129A>G		intron_variant	Intron 9 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49532 AN: 151944 Hom.: 8473 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.356 AC: 499038 AN: 1400486 Hom.: 90729 Cov.: 29 AF XY: 0.357 AC XY: 247582 AN XY: 694188

African (AFR) AF: 0.218 AC: 6903 AN: 31684

American (AMR) AF: 0.371 AC: 13840 AN: 37262

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 6500 AN: 23880

East Asian (EAS) AF: 0.370 AC: 14430 AN: 38996

South Asian (SAS) AF: 0.377 AC: 28962 AN: 76812

European-Finnish (FIN) AF: 0.412 AC: 21227 AN: 51514

Middle Eastern (MID) AF: 0.268 AC: 1475 AN: 5500

European-Non Finnish (NFE) AF: 0.358 AC: 385661 AN: 1077222

Other (OTH) AF: 0.348 AC: 20040 AN: 57616

GnomAD4 genome AF: 0.326 AC: 49534 AN: 152062 Hom.: 8475 Cov.: 32 AF XY: 0.331 AC XY: 24580 AN XY: 74310

African (AFR) AF: 0.224 AC: 9302 AN: 41500

American (AMR) AF: 0.364 AC: 5557 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3472

East Asian (EAS) AF: 0.393 AC: 2032 AN: 5170

South Asian (SAS) AF: 0.382 AC: 1830 AN: 4796

European-Finnish (FIN) AF: 0.403 AC: 4254 AN: 10548

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24492 AN: 67982

Other (OTH) AF: 0.338 AC: 712 AN: 2106

Alfa AF: 0.343 Hom.: 11631

Bravo AF: 0.317

Asia WGS AF: 0.389 AC: 1349 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	2.2
DANN	Benign	0.61
PhyloP100		0.26
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: rs3082; hg19: chr1-232002392; COSMIC: COSV64087002;