1-231636667-C-T

Variant names:

• chr1-231636667-C-T
• rs823162
• NM_018662.3:c.67+9733C>T

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+9733C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 152,232 control chromosomes in the GnomAD database, including 68,169 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 0.95 (68169 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.67+9733C>T		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.67+9733C>T		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.67+9733C>T		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.67+9733C>T		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.67+9733C>T		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000366633.7	TSL:1	c.67+9733C>T		intron	N/A	ENSP00000355593.3

Frequencies

GnomAD3 genomes AF: 0.946 AC: 143864 AN: 152114 Hom.: 68109 Cov.: 31

Gnomad AFR AF: 0.984

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.958

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.945

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

GnomAD4 genome AF: 0.946 AC: 143983 AN: 152232 Hom.: 68169 Cov.: 31 AF XY: 0.948 AC XY: 70525 AN XY: 74410

African (AFR) AF: 0.985 AC: 40890 AN: 41532

American (AMR) AF: 0.958 AC: 14644 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3252 AN: 3470

East Asian (EAS) AF: 0.994 AC: 5157 AN: 5186

South Asian (SAS) AF: 0.948 AC: 4561 AN: 4812

European-Finnish (FIN) AF: 0.950 AC: 10069 AN: 10596

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.917 AC: 62402 AN: 68024

Other (OTH) AF: 0.945 AC: 2000 AN: 2116

Alfa AF: 0.926 Hom.: 107297

Bravo AF: 0.948

Asia WGS AF: 0.967 AC: 3363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.38
PhyloP100		-0.18
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: rs823162; hg19: chr1-231772413;