1-231801734-T-C

Variant names:

• chr1-231801734-T-C
• rs2738864
• NM_018662.3:c.1792+1524T>C

Variant summary

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

The NM_001164537.2(DISC1):​c.1888+1524T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 152,046 control chromosomes in the GnomAD database, including 42,223 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 0.74 (42223 hom., cov: 31)
• Consequence: DISC1 NM_001164537.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 5 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]

ENSG00000286071 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164537.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	NM_018662.3	MANE Select	c.1792+1524T>C		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.1888+1524T>C		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.1792+1524T>C		intron	N/A	NP_001012975.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000439617.8	TSL:5 MANE Select	c.1792+1524T>C		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1792+1524T>C		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000366633.7	TSL:1	c.1792+1524T>C		intron	N/A	ENSP00000355593.3

Frequencies

GnomAD3 genomes AF: 0.744 AC: 112987 AN: 151930 Hom.: 42214 Cov.: 31

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.743 AC: 113043 AN: 152046 Hom.: 42223 Cov.: 31 AF XY: 0.746 AC XY: 55466 AN XY: 74328

African (AFR) AF: 0.713 AC: 29561 AN: 41432

American (AMR) AF: 0.783 AC: 11951 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2522 AN: 3472

East Asian (EAS) AF: 0.608 AC: 3144 AN: 5174

South Asian (SAS) AF: 0.758 AC: 3652 AN: 4816

European-Finnish (FIN) AF: 0.771 AC: 8155 AN: 10584

Middle Eastern (MID) AF: 0.723 AC: 211 AN: 292

European-Non Finnish (NFE) AF: 0.761 AC: 51712 AN: 67984

Other (OTH) AF: 0.750 AC: 1582 AN: 2110

Alfa AF: 0.752 Hom.: 6567

Bravo AF: 0.741

Asia WGS AF: 0.682 AC: 2372 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.41
DANN	Benign	0.82
PhyloP100		-1.0
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: rs2738864; hg19: chr1-231937480;