1-231896069-C-T

Variant names:

• chr1-231896069-C-T
• rs967433
• NM_018662.3:c.1982-62759C>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.1982-62759C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,892 control chromosomes in the GnomAD database, including 20,862 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 0.52 (20862 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 7 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	NM_018662.3	MANE Select	c.1982-62759C>T		intron	N/A	NP_061132.2	Q9NRI5-1
	DISC1	NM_001164537.2		c.2078-62759C>T		intron	N/A	NP_001158009.1	C4P096
	DISC1	NM_001012957.2		c.1982-62759C>T		intron	N/A	NP_001012975.1	Q9NRI5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000439617.8	TSL:5 MANE Select	c.1982-62759C>T		intron	N/A	ENSP00000403888.4	Q9NRI5-1
	DISC1	ENST00000366637.8	TSL:5	c.1982-62759C>T		intron	N/A	ENSP00000355597.6	Q9NRI5-2
	DISC1	ENST00000535983.5	TSL:1	c.1981+77552C>T		intron	N/A	ENSP00000443996.1	Q9NRI5-8

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79121 AN: 151774 Hom.: 20859 Cov.: 31

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.521 AC: 79153 AN: 151892 Hom.: 20862 Cov.: 31 AF XY: 0.525 AC XY: 38980 AN XY: 74218

African (AFR) AF: 0.457 AC: 18903 AN: 41396

American (AMR) AF: 0.493 AC: 7511 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1803 AN: 3470

East Asian (EAS) AF: 0.621 AC: 3202 AN: 5160

South Asian (SAS) AF: 0.589 AC: 2836 AN: 4818

European-Finnish (FIN) AF: 0.620 AC: 6542 AN: 10550

Middle Eastern (MID) AF: 0.558 AC: 163 AN: 292

European-Non Finnish (NFE) AF: 0.538 AC: 36536 AN: 67932

Other (OTH) AF: 0.521 AC: 1101 AN: 2112

Alfa AF: 0.528 Hom.: 82150

Bravo AF: 0.504

Asia WGS AF: 0.576 AC: 2000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.18
DANN	Benign	0.60
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: rs967433; hg19: chr1-232031815;