chr1-231872014-G-A

Variant names:

• chr1-231872014-G-A
• rs9431706
• NM_018662.3:c.1981+53497G>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.1981+53497G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,004 control chromosomes in the GnomAD database, including 19,142 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 0.50 (19142 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.524 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+53497G>A		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.2077+53497G>A		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.1981+53497G>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+53497G>A		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1981+53497G>A		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000535983.5	TSL:1	c.1981+53497G>A		intron	N/A	ENSP00000443996.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75912 AN: 151886 Hom.: 19125 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.500 AC: 75972 AN: 152004 Hom.: 19142 Cov.: 32 AF XY: 0.499 AC XY: 37058 AN XY: 74278

African (AFR) AF: 0.529 AC: 21956 AN: 41466

American (AMR) AF: 0.521 AC: 7968 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1828 AN: 3472

East Asian (EAS) AF: 0.485 AC: 2500 AN: 5152

South Asian (SAS) AF: 0.518 AC: 2492 AN: 4810

European-Finnish (FIN) AF: 0.429 AC: 4521 AN: 10550

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33088 AN: 67948

Other (OTH) AF: 0.495 AC: 1045 AN: 2110

Alfa AF: 0.486 Hom.: 2232

Bravo AF: 0.507

Asia WGS AF: 0.480 AC: 1671 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	2.5
DANN	Benign	0.84
PhyloP100		0.080
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: rs9431706; hg19: chr1-232007760;