rs3082

Positions:

• chr1-231866646-A-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1981+48129A>G		intron_variant		ENST00000439617.8	NP_061132.2
TSNAX-DISC1	NR_028393.1	n.2647+48129A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1981+48129A>G		intron_variant		5	NM_018662.3	ENSP00000403888	A2

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

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.371

Gnomad4 ASJ exome AF: 0.272

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.377

Gnomad4 FIN exome AF: 0.412

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.348

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

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.338

Alfa AF: 0.346 Hom.: 9040

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3082; hg19: chr1-232002392; COSMIC: COSV64087002;