1-231727458-T-C

Variant names:

• chr1-231727458-T-C
• rs2487453
• NM_018662.3:c.1118-22468T>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.1118-22468T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 151,826 control chromosomes in the GnomAD database, including 28,566 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 0.61 (28566 hom., cov: 30)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1118-22468T>C		intron_variant	Intron 3 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1118-22468T>C		intron_variant	Intron 3 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1118-22468T>C		intron_variant	Intron 3 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.*979-22468T>C		intron_variant	Intron 7 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92202 AN: 151708 Hom.: 28551 Cov.: 30

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.608 AC: 92247 AN: 151826 Hom.: 28566 Cov.: 30 AF XY: 0.614 AC XY: 45536 AN XY: 74170

African (AFR) AF: 0.484 AC: 20029 AN: 41404

American (AMR) AF: 0.640 AC: 9774 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2306 AN: 3472

East Asian (EAS) AF: 0.592 AC: 3010 AN: 5084

South Asian (SAS) AF: 0.714 AC: 3431 AN: 4808

European-Finnish (FIN) AF: 0.680 AC: 7167 AN: 10544

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44431 AN: 67936

Other (OTH) AF: 0.585 AC: 1230 AN: 2104

Alfa AF: 0.637 Hom.: 50351

Bravo AF: 0.595

Asia WGS AF: 0.631 AC: 2192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.68
PhyloP100		-0.048
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2487453; hg19: chr1-231863204;