NM_018662.3:c.2043-6132T>G

Variant names:

• chr1-232002653-T-G
• rs1772702
• NM_018662.3:c.2043-6132T>G

Variant summary

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

The NM_018662.3(DISC1):​c.2043-6132T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 150,528 control chromosomes in the GnomAD database, including 17,030 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 0.43 (17030 hom., cov: 30)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 1 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018662.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	NM_018662.3	MANE Select	c.2043-6132T>G		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.2139-6132T>G		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.2043-6132T>G		intron	N/A	NP_001012975.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000439617.8	TSL:5 MANE Select	c.2043-6132T>G		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.2043-6132T>G		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000535983.5	TSL:1	c.1982-6132T>G		intron	N/A	ENSP00000443996.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 64611 AN: 150410 Hom.: 16991 Cov.: 30

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.430 AC: 64701 AN: 150528 Hom.: 17030 Cov.: 30 AF XY: 0.427 AC XY: 31353 AN XY: 73408

African (AFR) AF: 0.751 AC: 30813 AN: 41052

American (AMR) AF: 0.244 AC: 3671 AN: 15064

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1057 AN: 3450

East Asian (EAS) AF: 0.240 AC: 1218 AN: 5074

South Asian (SAS) AF: 0.412 AC: 1955 AN: 4748

European-Finnish (FIN) AF: 0.346 AC: 3539 AN: 10220

Middle Eastern (MID) AF: 0.313 AC: 90 AN: 288

European-Non Finnish (NFE) AF: 0.313 AC: 21148 AN: 67640

Other (OTH) AF: 0.370 AC: 772 AN: 2084

Alfa AF: 0.376 Hom.: 1562

Bravo AF: 0.430

Asia WGS AF: 0.364 AC: 1267 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.54
DANN	Benign	0.54
PhyloP100		-1.3
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: rs1772702; hg19: chr1-232138399;