rs12740724

Variant names:

• chr1-231880880-A-G
• rs12740724
• NM_018662.3:c.1981+62363A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-231880880-A-G
• chr1-231880880-A-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+62363A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,898 control chromosomes in the GnomAD database, including 8,942 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 (8942 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1981+62363A>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+62363A>G		intron_variant	Intron 9 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1981+62363A>G		intron_variant	Intron 9 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51599 AN: 151780 Hom.: 8945 Cov.: 31

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.340 AC: 51613 AN: 151898 Hom.: 8942 Cov.: 31 AF XY: 0.340 AC XY: 25237 AN XY: 74218

African (AFR) AF: 0.281 AC: 11626 AN: 41420

American (AMR) AF: 0.362 AC: 5517 AN: 15248

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

East Asian (EAS) AF: 0.165 AC: 850 AN: 5164

South Asian (SAS) AF: 0.356 AC: 1710 AN: 4808

European-Finnish (FIN) AF: 0.353 AC: 3724 AN: 10542

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25444 AN: 67934

Other (OTH) AF: 0.341 AC: 719 AN: 2106

Alfa AF: 0.352 Hom.: 1155

Bravo AF: 0.334

Asia WGS AF: 0.233 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		-0.55
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: rs12740724; hg19: chr1-232016626;