rs821639

Variant names:

• chr1-232014097-A-G
• rs821639
• NM_018662.3:c.2307+5048A>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.2307+5048A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,020 control chromosomes in the GnomAD database, including 7,816 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 0.32 (7816 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 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.2307+5048A>G		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.2403+5048A>G		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.2241+5114A>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.2307+5048A>G		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.2241+5114A>G		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000622252.4	TSL:5	c.*848+5048A>G		intron	N/A	ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47940 AN: 151900 Hom.: 7797 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.316 AC: 48012 AN: 152020 Hom.: 7816 Cov.: 32 AF XY: 0.318 AC XY: 23613 AN XY: 74296

African (AFR) AF: 0.331 AC: 13721 AN: 41450

American (AMR) AF: 0.256 AC: 3909 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 845 AN: 3470

East Asian (EAS) AF: 0.182 AC: 942 AN: 5162

South Asian (SAS) AF: 0.291 AC: 1400 AN: 4816

European-Finnish (FIN) AF: 0.438 AC: 4618 AN: 10540

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.317 AC: 21580 AN: 67984

Other (OTH) AF: 0.287 AC: 607 AN: 2112

Alfa AF: 0.309 Hom.: 31156

Bravo AF: 0.303

Asia WGS AF: 0.269 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.4
DANN	Benign	0.82
PhyloP100		1.9
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: rs821639; hg19: chr1-232149843; COSMIC: COSV64093965; COSMIC: COSV64093965;