NM_018662.3:c.1981+53431A>G

Variant names:

• chr1-231871948-A-G
• rs1015101
• NM_018662.3:c.1981+53431A>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+53431A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,034 control chromosomes in the GnomAD database, including 11,497 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 0.38 (11497 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1981+53431A>G		intron_variant	Intron 9 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1981+53431A>G		intron_variant	Intron 9 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1981+53431A>G		intron_variant	Intron 9 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58496 AN: 151914 Hom.: 11488 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.385 AC: 58533 AN: 152034 Hom.: 11497 Cov.: 32 AF XY: 0.388 AC XY: 28806 AN XY: 74300

African (AFR) AF: 0.332 AC: 13771 AN: 41470

American (AMR) AF: 0.400 AC: 6121 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1278 AN: 3472

East Asian (EAS) AF: 0.511 AC: 2631 AN: 5148

South Asian (SAS) AF: 0.415 AC: 1999 AN: 4820

European-Finnish (FIN) AF: 0.442 AC: 4667 AN: 10562

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26798 AN: 67964

Other (OTH) AF: 0.399 AC: 843 AN: 2112

Alfa AF: 0.392 Hom.: 5628

Bravo AF: 0.379

Asia WGS AF: 0.474 AC: 1644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.71
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: rs1015101; hg19: chr1-232007694;