chr1-231741236-G-A

Variant names:

• chr1-231741236-G-A
• rs2793094
• NM_018662.3:c.1118-8690G>A

Variant summary

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

The NM_018662.3(DISC1):​c.1118-8690G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.967 in 152,308 control chromosomes in the GnomAD database, including 71,406 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 0.97 (71406 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.422
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.1118-8690G>A		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.1118-4168G>A		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.1118-8690G>A		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.1118-8690G>A		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1118-8690G>A		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000366633.7	TSL:1	c.1118-8690G>A		intron	N/A	ENSP00000355593.3

Frequencies

GnomAD3 genomes AF: 0.967 AC: 147205 AN: 152190 Hom.: 71363 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.989

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.994

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.977

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

GnomAD4 genome AF: 0.967 AC: 147304 AN: 152308 Hom.: 71406 Cov.: 32 AF XY: 0.968 AC XY: 72077 AN XY: 74472

African (AFR) AF: 0.886 AC: 36788 AN: 41534

American (AMR) AF: 0.989 AC: 15133 AN: 15308

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3470 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 1.00 AC: 4829 AN: 4830

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

Middle Eastern (MID) AF: 0.993 AC: 292 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68010 AN: 68042

Other (OTH) AF: 0.977 AC: 2068 AN: 2116

Alfa AF: 0.989 Hom.: 119725

Bravo AF: 0.962

Asia WGS AF: 0.992 AC: 3451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.42
DANN	Benign	0.60
PhyloP100		-0.42
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: rs2793094; hg19: chr1-231876982;