rs9432028

Variant names:

• chr1-231873364-G-A
• rs9432028
• NM_018662.3:c.1981+54847G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-231873364-G-A
• chr1-231873364-G-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.1981+54847G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,114 control chromosomes in the GnomAD database, including 9,034 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 0.34 (9034 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 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.1981+54847G>A		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.2077+54847G>A		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.1981+54847G>A		intron	N/A	NP_001012975.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000439617.8	TSL:5 MANE Select	c.1981+54847G>A		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1981+54847G>A		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000535983.5	TSL:1	c.1981+54847G>A		intron	N/A	ENSP00000443996.1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51920 AN: 151996 Hom.: 9036 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.341 AC: 51933 AN: 152114 Hom.: 9034 Cov.: 32 AF XY: 0.342 AC XY: 25397 AN XY: 74352

African (AFR) AF: 0.285 AC: 11819 AN: 41498

American (AMR) AF: 0.363 AC: 5554 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1522 AN: 3470

East Asian (EAS) AF: 0.166 AC: 857 AN: 5172

South Asian (SAS) AF: 0.357 AC: 1722 AN: 4818

European-Finnish (FIN) AF: 0.354 AC: 3743 AN: 10576

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25489 AN: 67984

Other (OTH) AF: 0.344 AC: 725 AN: 2110

Alfa AF: 0.226 Hom.: 566

Bravo AF: 0.336

Asia WGS AF: 0.234 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.68
PhyloP100		-2.5
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: rs9432028; hg19: chr1-232009110;