NM_018662.3:c.68-10522T>C

Variant names:

• chr1-231683304-T-C
• rs1417584
• NM_018662.3:c.68-10522T>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.68-10522T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,826 control chromosomes in the GnomAD database, including 18,528 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 0.49 (18528 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450
• Publications: 17 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.68-10522T>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.68-10522T>C		intron_variant	Intron 1 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.68-10522T>C		intron_variant	Intron 1 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.496-10522T>C		intron_variant	Intron 5 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73666 AN: 151708 Hom.: 18492 Cov.: 31

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.486 AC: 73759 AN: 151826 Hom.: 18528 Cov.: 31 AF XY: 0.488 AC XY: 36227 AN XY: 74190

African (AFR) AF: 0.536 AC: 22160 AN: 41372

American (AMR) AF: 0.548 AC: 8354 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1633 AN: 3468

East Asian (EAS) AF: 0.840 AC: 4347 AN: 5172

South Asian (SAS) AF: 0.489 AC: 2352 AN: 4806

European-Finnish (FIN) AF: 0.439 AC: 4609 AN: 10502

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28908 AN: 67944

Other (OTH) AF: 0.488 AC: 1026 AN: 2104

Alfa AF: 0.446 Hom.: 26447

Bravo AF: 0.499

Asia WGS AF: 0.633 AC: 2202 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.47
PhyloP100		-0.45
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: rs1417584; hg19: chr1-231819050;