rs2082552

Variant names:

• chr1-231632144-T-C
• rs2082552
• NM_018662.3:c.67+5210T>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.67+5210T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,216 control chromosomes in the GnomAD database, including 3,033 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 0.17 (3033 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 8 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.67+5210T>C		intron_variant	Intron 1 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.67+5210T>C		intron_variant	Intron 1 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.67+5210T>C		intron_variant	Intron 1 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.496-61682T>C		intron_variant	Intron 5 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25574 AN: 152098 Hom.: 3033 Cov.: 32

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.168 AC: 25571 AN: 152216 Hom.: 3033 Cov.: 32 AF XY: 0.174 AC XY: 12953 AN XY: 74420

African (AFR) AF: 0.0425 AC: 1766 AN: 41562

American (AMR) AF: 0.314 AC: 4796 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 792 AN: 3470

East Asian (EAS) AF: 0.491 AC: 2539 AN: 5174

South Asian (SAS) AF: 0.163 AC: 789 AN: 4830

European-Finnish (FIN) AF: 0.215 AC: 2279 AN: 10586

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12077 AN: 67992

Other (OTH) AF: 0.183 AC: 386 AN: 2114

Alfa AF: 0.178 Hom.: 5325

Bravo AF: 0.172

Asia WGS AF: 0.258 AC: 896 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.8
DANN	Benign	0.47
PhyloP100		0.21
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: rs2082552; hg19: chr1-231767890;