chr1-231812900-G-A

Variant names:

• chr1-231812900-G-A
• rs967244
• NM_018662.3:c.1793-5429G>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.1793-5429G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 152,166 control chromosomes in the GnomAD database, including 50,411 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 0.81 (50411 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 11 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.813 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.1793-5429G>A		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.1889-5429G>A		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.1793-5429G>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.1793-5429G>A		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1793-5429G>A		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000366633.7	TSL:1	c.1793-5429G>A		intron	N/A	ENSP00000355593.3

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123729 AN: 152046 Hom.: 50366 Cov.: 32

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.807

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

GnomAD4 genome AF: 0.814 AC: 123833 AN: 152166 Hom.: 50411 Cov.: 32 AF XY: 0.814 AC XY: 60528 AN XY: 74400

African (AFR) AF: 0.803 AC: 33352 AN: 41520

American (AMR) AF: 0.822 AC: 12573 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2883 AN: 3470

East Asian (EAS) AF: 0.809 AC: 4178 AN: 5166

South Asian (SAS) AF: 0.745 AC: 3590 AN: 4818

European-Finnish (FIN) AF: 0.847 AC: 8969 AN: 10584

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.819 AC: 55681 AN: 67992

Other (OTH) AF: 0.808 AC: 1705 AN: 2110

Alfa AF: 0.813 Hom.: 215833

Bravo AF: 0.811

Asia WGS AF: 0.786 AC: 2737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.7
DANN	Benign	0.28
PhyloP100		1.3
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: rs967244; hg19: chr1-231948646;