rs1538979

Variant names:

• chr1-231761122-C-T
• rs1538979
• NM_018662.3:c.1269-6018C>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.1269-6018C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 151,974 control chromosomes in the GnomAD database, including 3,300 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 0.19 (3300 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 18 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1269-6018C>T		intron_variant	Intron 4 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1269-6018C>T		intron_variant	Intron 4 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1269-6018C>T		intron_variant	Intron 4 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.*1130-6018C>T		intron_variant	Intron 8 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29499 AN: 151856 Hom.: 3293 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.191

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.194 AC: 29550 AN: 151974 Hom.: 3300 Cov.: 32 AF XY: 0.196 AC XY: 14587 AN XY: 74314

African (AFR) AF: 0.305 AC: 12625 AN: 41406

American (AMR) AF: 0.180 AC: 2755 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 477 AN: 3466

East Asian (EAS) AF: 0.235 AC: 1211 AN: 5162

South Asian (SAS) AF: 0.248 AC: 1193 AN: 4816

European-Finnish (FIN) AF: 0.101 AC: 1067 AN: 10550

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.141 AC: 9611 AN: 67982

Other (OTH) AF: 0.207 AC: 439 AN: 2116

Alfa AF: 0.163 Hom.: 2745

Bravo AF: 0.205

Asia WGS AF: 0.219 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.64
DANN	Benign	0.75
PhyloP100		-0.11
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: rs1538979; hg19: chr1-231896868;