rs17820909

Variant names:

• chr1-231882239-A-G
• rs17820909
• NM_018662.3:c.1981+63722A>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.1981+63722A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.056 in 152,292 control chromosomes in the GnomAD database, including 327 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 0.056 (327 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0745 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.1981+63722A>G		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.2077+63722A>G		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.1981+63722A>G		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.1981+63722A>G		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1981+63722A>G		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000535983.5	TSL:1	c.1981+63722A>G		intron	N/A	ENSP00000443996.1

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8522 AN: 152174 Hom.: 327 Cov.: 32

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0775

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.0903

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0762

Gnomad OTH AF: 0.0454

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

GnomAD4 genome AF: 0.0560 AC: 8523 AN: 152292 Hom.: 327 Cov.: 32 AF XY: 0.0556 AC XY: 4140 AN XY: 74450

African (AFR) AF: 0.0156 AC: 649 AN: 41566

American (AMR) AF: 0.0774 AC: 1184 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0746 AC: 259 AN: 3472

East Asian (EAS) AF: 0.00424 AC: 22 AN: 5188

South Asian (SAS) AF: 0.0239 AC: 115 AN: 4818

European-Finnish (FIN) AF: 0.0903 AC: 958 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0762 AC: 5184 AN: 68018

Other (OTH) AF: 0.0449 AC: 95 AN: 2116

Alfa AF: 0.0694 Hom.: 92

Bravo AF: 0.0543

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.66
PhyloP100		0.63
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: rs17820909; hg19: chr1-232017985;