NM_018662.3:c.2307+2299T>C

Variant names:

• chr1-232011348-T-C
• rs821624
• NM_018662.3:c.2307+2299T>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.2307+2299T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,998 control chromosomes in the GnomAD database, including 20,871 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 0.48 (20871 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.2307+2299T>C		intron_variant	Intron 11 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.2307+2299T>C		intron_variant	Intron 11 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.2241+2365T>C		intron_variant	Intron 11 of 12	5		ENSP00000355597.6
DISC1	ENST00000622252.4	c.*848+2299T>C		intron_variant	Intron 10 of 11	5		ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73573 AN: 151880 Hom.: 20831 Cov.: 31

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.485 AC: 73655 AN: 151998 Hom.: 20871 Cov.: 31 AF XY: 0.483 AC XY: 35892 AN XY: 74292

African (AFR) AF: 0.801 AC: 33212 AN: 41478

American (AMR) AF: 0.327 AC: 5002 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1280 AN: 3468

East Asian (EAS) AF: 0.440 AC: 2269 AN: 5158

South Asian (SAS) AF: 0.478 AC: 2293 AN: 4796

European-Finnish (FIN) AF: 0.372 AC: 3927 AN: 10556

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24188 AN: 67946

Other (OTH) AF: 0.426 AC: 900 AN: 2112

Alfa AF: 0.424 Hom.: 1954

Bravo AF: 0.492

Asia WGS AF: 0.484 AC: 1682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.1
DANN	Benign	0.83
PhyloP100		-0.77
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: rs821624; hg19: chr1-232147094; COSMIC: COSV64093896; COSMIC: COSV64093896;