rs1535529

Variant names:

• chr1-231818863-G-A
• rs1535529
• ENST00000602281.5:c.*338G>A

Variant summary

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

The NM_001164544.2(DISC1):​c.*338G>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 0.237 in 1,093,810 control chromosomes in the GnomAD database, including 31,362 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 0.23 (4390 hom., cov: 33)
  • Exomes 𝑓: 0.24 (26972 hom.)
• Consequence: DISC1 NM_001164544.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740
• Publications: 6 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:):

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 = 0.373 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164544.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	NM_018662.3	MANE Select	c.1981+346G>A		intron	N/A	NP_061132.2
	DISC1	NM_001164544.2		c.*338G>A		3_prime_UTR	Exon 9 of 9	NP_001158016.1
	DISC1	NM_001164545.2		c.*484G>A		3_prime_UTR	Exon 8 of 8	NP_001158017.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000602281.5	TSL:1	c.*338G>A		3_prime_UTR	Exon 9 of 9	ENSP00000473425.1
	DISC1	ENST00000539444.5	TSL:1	c.*484G>A		3_prime_UTR	Exon 8 of 8	ENSP00000440953.1
	DISC1	ENST00000602873.5	TSL:1	c.*513G>A		3_prime_UTR	Exon 5 of 5	ENSP00000473386.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35499 AN: 151964 Hom.: 4378 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.238 AC: 223703 AN: 941728 Hom.: 26972 Cov.: 36 AF XY: 0.239 AC XY: 105293 AN XY: 441394

African (AFR) AF: 0.171 AC: 3232 AN: 18884

American (AMR) AF: 0.252 AC: 1408 AN: 5578

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 1836 AN: 7972

East Asian (EAS) AF: 0.402 AC: 3561 AN: 8868

South Asian (SAS) AF: 0.272 AC: 8343 AN: 30618

European-Finnish (FIN) AF: 0.316 AC: 1785 AN: 5644

Middle Eastern (MID) AF: 0.208 AC: 426 AN: 2050

European-Non Finnish (NFE) AF: 0.236 AC: 195200 AN: 828758

Other (OTH) AF: 0.237 AC: 7912 AN: 33356

GnomAD4 genome AF: 0.234 AC: 35527 AN: 152082 Hom.: 4390 Cov.: 33 AF XY: 0.238 AC XY: 17707 AN XY: 74330

African (AFR) AF: 0.182 AC: 7557 AN: 41478

American (AMR) AF: 0.219 AC: 3344 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 768 AN: 3472

East Asian (EAS) AF: 0.387 AC: 2001 AN: 5174

South Asian (SAS) AF: 0.286 AC: 1377 AN: 4822

European-Finnish (FIN) AF: 0.334 AC: 3529 AN: 10562

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16356 AN: 67984

Other (OTH) AF: 0.214 AC: 451 AN: 2108

Alfa AF: 0.234 Hom.: 11879

Bravo AF: 0.221

Asia WGS AF: 0.315 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.7
DANN	Benign	0.64
PhyloP100		0.074
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1535529; hg19: chr1-231954609;