1-231966518-G-A

Variant names:

• chr1-231966518-G-A
• rs821597
• NM_018662.3:c.2042+7630G>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.2042+7630G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 152,142 control chromosomes in the GnomAD database, including 20,358 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 0.48 (20358 hom., cov: 33)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• Publications: 34 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.2042+7630G>A		intron_variant	Intron 10 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.2042+7630G>A		intron_variant	Intron 10 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.2042+7630G>A		intron_variant	Intron 10 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72970 AN: 152024 Hom.: 20312 Cov.: 33

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.480 AC: 73060 AN: 152142 Hom.: 20358 Cov.: 33 AF XY: 0.480 AC XY: 35670 AN XY: 74362

African (AFR) AF: 0.786 AC: 32642 AN: 41526

American (AMR) AF: 0.331 AC: 5053 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1282 AN: 3472

East Asian (EAS) AF: 0.447 AC: 2312 AN: 5174

South Asian (SAS) AF: 0.466 AC: 2244 AN: 4818

European-Finnish (FIN) AF: 0.386 AC: 4082 AN: 10574

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23974 AN: 67980

Other (OTH) AF: 0.423 AC: 894 AN: 2112

Alfa AF: 0.391 Hom.: 33321

Bravo AF: 0.487

Asia WGS AF: 0.495 AC: 1722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.80
DANN	Benign	0.25
PhyloP100		0.065
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: rs821597; hg19: chr1-232102264; COSMIC: COSV64093663;