1-231924059-G-T

Variant names:

• chr1-231924059-G-T
• rs821717
• NM_018662.3:c.1982-34769G>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.1982-34769G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 152,220 control chromosomes in the GnomAD database, including 52,713 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 0.83 (52713 hom., cov: 33)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 5 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 = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1982-34769G>T		intron_variant	Intron 9 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1982-34769G>T		intron_variant	Intron 9 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1982-34769G>T		intron_variant	Intron 9 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126367 AN: 152102 Hom.: 52669 Cov.: 33

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.790

Gnomad OTH AF: 0.828

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

GnomAD4 genome AF: 0.831 AC: 126469 AN: 152220 Hom.: 52713 Cov.: 33 AF XY: 0.830 AC XY: 61797 AN XY: 74416

African (AFR) AF: 0.880 AC: 36535 AN: 41534

American (AMR) AF: 0.877 AC: 13424 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 2856 AN: 3470

East Asian (EAS) AF: 0.917 AC: 4742 AN: 5170

South Asian (SAS) AF: 0.860 AC: 4147 AN: 4824

European-Finnish (FIN) AF: 0.792 AC: 8392 AN: 10598

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.790 AC: 53719 AN: 68008

Other (OTH) AF: 0.827 AC: 1746 AN: 2112

Alfa AF: 0.801 Hom.: 87896

Bravo AF: 0.839

Asia WGS AF: 0.859 AC: 2988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.71
PhyloP100		0.055
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: rs821717; hg19: chr1-232059805;