1-232013187-T-C

Variant names:

• chr1-232013187-T-C
• rs821633
• NM_018662.3:c.2307+4138T>C

Variant summary

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

The NM_018662.3(DISC1):​c.2307+4138T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,920 control chromosomes in the GnomAD database, including 11,062 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 0.37 (11062 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.729
• Publications: 13 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.2307+4138T>C		intron_variant	Intron 11 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.2307+4138T>C		intron_variant	Intron 11 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.2241+4204T>C		intron_variant	Intron 11 of 12	5		ENSP00000355597.6
DISC1	ENST00000622252.4	c.*848+4138T>C		intron_variant	Intron 10 of 11	5		ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56840 AN: 151802 Hom.: 11041 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.375 AC: 56914 AN: 151920 Hom.: 11062 Cov.: 32 AF XY: 0.381 AC XY: 28276 AN XY: 74264

African (AFR) AF: 0.441 AC: 18272 AN: 41402

American (AMR) AF: 0.354 AC: 5410 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 878 AN: 3466

East Asian (EAS) AF: 0.426 AC: 2196 AN: 5150

South Asian (SAS) AF: 0.387 AC: 1862 AN: 4810

European-Finnish (FIN) AF: 0.470 AC: 4971 AN: 10566

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22199 AN: 67936

Other (OTH) AF: 0.343 AC: 724 AN: 2108

Alfa AF: 0.349 Hom.: 13692

Bravo AF: 0.370

Asia WGS AF: 0.411 AC: 1430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.4
DANN	Benign	0.66
PhyloP100		-0.73
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: rs821633; hg19: chr1-232148933;