1-231793329-A-G

Variant names:

• chr1-231793329-A-G
• rs1322783
• NM_018662.3:c.1635-1913A>G

Variant summary

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

The NM_018662.3(DISC1):​c.1635-1913A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,144 control chromosomes in the GnomAD database, including 55,559 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 0.85 (55559 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55
• Publications: 9 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1635-1913A>G		intron_variant	Intron 6 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1635-1913A>G		intron_variant	Intron 6 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1635-1913A>G		intron_variant	Intron 6 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.*1496-1913A>G		intron_variant	Intron 10 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129845 AN: 152026 Hom.: 55531 Cov.: 32

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.902

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.865

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

GnomAD4 genome AF: 0.854 AC: 129924 AN: 152144 Hom.: 55559 Cov.: 32 AF XY: 0.857 AC XY: 63719 AN XY: 74356

African (AFR) AF: 0.823 AC: 34137 AN: 41502

American (AMR) AF: 0.901 AC: 13783 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3017 AN: 3470

East Asian (EAS) AF: 0.882 AC: 4558 AN: 5170

South Asian (SAS) AF: 0.902 AC: 4356 AN: 4828

European-Finnish (FIN) AF: 0.872 AC: 9215 AN: 10564

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.855 AC: 58128 AN: 68004

Other (OTH) AF: 0.863 AC: 1824 AN: 2114

Alfa AF: 0.857 Hom.: 76551

Bravo AF: 0.853

Asia WGS AF: 0.899 AC: 3127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.096
DANN	Benign	0.38
PhyloP100		-3.5
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: rs1322783; hg19: chr1-231929075;