1-231783095-C-T

Variant names:

• chr1-231783095-C-T
• rs4658945
• NM_018662.3:c.1634+12025C>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.1634+12025C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,940 control chromosomes in the GnomAD database, including 27,543 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 0.60 (27543 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• 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]

ENSG00000286071 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.66 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.1634+12025C>T		intron	N/A	NP_061132.2	Q9NRI5-1
	DISC1	NM_001164537.2		c.1730+12025C>T		intron	N/A	NP_001158009.1	C4P096
	DISC1	NM_001012957.2		c.1634+12025C>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.1634+12025C>T		intron	N/A	ENSP00000403888.4	Q9NRI5-1
	DISC1	ENST00000366637.8	TSL:5	c.1634+12025C>T		intron	N/A	ENSP00000355597.6	Q9NRI5-2
	DISC1	ENST00000366633.7	TSL:1	c.1634+12025C>T		intron	N/A	ENSP00000355593.3	Q9NRI5-5

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90696 AN: 151824 Hom.: 27529 Cov.: 31

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.597 AC: 90760 AN: 151940 Hom.: 27543 Cov.: 31 AF XY: 0.602 AC XY: 44725 AN XY: 74252

African (AFR) AF: 0.658 AC: 27280 AN: 41432

American (AMR) AF: 0.671 AC: 10235 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1876 AN: 3470

East Asian (EAS) AF: 0.599 AC: 3092 AN: 5162

South Asian (SAS) AF: 0.657 AC: 3158 AN: 4808

European-Finnish (FIN) AF: 0.583 AC: 6137 AN: 10530

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.547 AC: 37178 AN: 67966

Other (OTH) AF: 0.593 AC: 1253 AN: 2112

Alfa AF: 0.686 Hom.: 62128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.64
DANN	Benign	0.70
PhyloP100		-0.51
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: rs4658945; hg19: chr1-231918841;