chr1-231892165-G-T

Variant names:

• chr1-231892165-G-T
• rs1407599
• NM_018662.3:c.1982-66663G>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.1982-66663G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,048 control chromosomes in the GnomAD database, including 7,371 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 0.31 (7371 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190
• 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]

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 = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1982-66663G>T		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.1982-66663G>T		intron_variant	Intron 9 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1982-66663G>T		intron_variant	Intron 9 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46685 AN: 151930 Hom.: 7371 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.307 AC: 46689 AN: 152048 Hom.: 7371 Cov.: 32 AF XY: 0.307 AC XY: 22821 AN XY: 74322

African (AFR) AF: 0.260 AC: 10786 AN: 41478

American (AMR) AF: 0.293 AC: 4474 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1018 AN: 3470

East Asian (EAS) AF: 0.103 AC: 534 AN: 5178

South Asian (SAS) AF: 0.302 AC: 1455 AN: 4824

European-Finnish (FIN) AF: 0.376 AC: 3964 AN: 10552

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23403 AN: 67966

Other (OTH) AF: 0.304 AC: 642 AN: 2114

Alfa AF: 0.328 Hom.: 1492

Bravo AF: 0.297

Asia WGS AF: 0.209 AC: 729 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	1.9
DANN	Benign	0.62
PhyloP100		0.19
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: rs1407599; hg19: chr1-232027911; COSMIC: COSV64093600;