NM_018662.3:c.1982-32754A>C

Variant names:

• chr1-231926074-A-C
• rs7546310
• NM_018662.3:c.1982-32754A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018662.3(DISC1):​c.1982-32754A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,108 control chromosomes in the GnomAD database, including 17,899 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 0.47 (17899 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 6 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]

DISC1-IT1 (HGNC:41325): (DISC1 intronic transcript 1)

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 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.1982-32754A>C		intron	N/A	NP_061132.2	Q9NRI5-1
	DISC1	NM_001164537.2		c.2078-32754A>C		intron	N/A	NP_001158009.1	C4P096
	DISC1	NM_001012957.2		c.1982-32754A>C		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.1982-32754A>C		intron	N/A	ENSP00000403888.4	Q9NRI5-1
	DISC1	ENST00000366637.8	TSL:5	c.1982-32754A>C		intron	N/A	ENSP00000355597.6	Q9NRI5-2
	DISC1	ENST00000535983.5	TSL:1	c.1982-82711A>C		intron	N/A	ENSP00000443996.1	Q9NRI5-8

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71164 AN: 151986 Hom.: 17893 Cov.: 33

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.467

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.468 AC: 71178 AN: 152104 Hom.: 17899 Cov.: 33 AF XY: 0.464 AC XY: 34524 AN XY: 74358

African (AFR) AF: 0.303 AC: 12574 AN: 41494

American (AMR) AF: 0.489 AC: 7478 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1690 AN: 3470

East Asian (EAS) AF: 0.208 AC: 1077 AN: 5176

South Asian (SAS) AF: 0.472 AC: 2276 AN: 4826

European-Finnish (FIN) AF: 0.579 AC: 6117 AN: 10564

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38438 AN: 67980

Other (OTH) AF: 0.462 AC: 976 AN: 2112

Alfa AF: 0.409 Hom.: 4783

Bravo AF: 0.454

Asia WGS AF: 0.331 AC: 1153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.78
DANN	Benign	0.48
PhyloP100		-0.34
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: rs7546310; hg19: chr1-232061820;