rs821722

Variant names:

• chr1-231900284-G-A
• rs821722
• NM_018662.3:c.1982-58544G>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.1982-58544G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,030 control chromosomes in the GnomAD database, including 15,276 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 0.43 (15276 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292
• 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]

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 (EAS) allele frequency at 95% confidence interval = 0.737 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.1982-58544G>A		intron	N/A	NP_061132.2	Q9NRI5-1
	DISC1	NM_001164537.2		c.2078-58544G>A		intron	N/A	NP_001158009.1	C4P096
	DISC1	NM_001012957.2		c.1982-58544G>A		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.1982-58544G>A		intron	N/A	ENSP00000403888.4	Q9NRI5-1
	DISC1	ENST00000366637.8	TSL:5	c.1982-58544G>A		intron	N/A	ENSP00000355597.6	Q9NRI5-2
	DISC1	ENST00000535983.5	TSL:1	c.1981+81767G>A		intron	N/A	ENSP00000443996.1	Q9NRI5-8

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66052 AN: 151912 Hom.: 15251 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.435 AC: 66119 AN: 152030 Hom.: 15276 Cov.: 32 AF XY: 0.434 AC XY: 32257 AN XY: 74302

African (AFR) AF: 0.520 AC: 21572 AN: 41452

American (AMR) AF: 0.496 AC: 7577 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1654 AN: 3472

East Asian (EAS) AF: 0.757 AC: 3918 AN: 5176

South Asian (SAS) AF: 0.473 AC: 2275 AN: 4814

European-Finnish (FIN) AF: 0.268 AC: 2831 AN: 10564

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25045 AN: 67962

Other (OTH) AF: 0.460 AC: 967 AN: 2104

Alfa AF: 0.405 Hom.: 33615

Bravo AF: 0.459

Asia WGS AF: 0.558 AC: 1937 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.57
PhyloP100		-0.29
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: rs821722; hg19: chr1-232036030;