chr1-232040449-G-T

Variant names:

• chr1-232040449-G-T
• rs980989
• NM_018662.3:c.*3618G>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.*3618G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,054 control chromosomes in the GnomAD database, including 2,987 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 (2987 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: DISC1 NM_018662.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520
• Publications: 16 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.*3618G>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.*3618G>T		3_prime_UTR_variant	Exon 13 of 13	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.*3618G>T		3_prime_UTR_variant	Exon 13 of 13	5		ENSP00000355597.6
DISC1	ENST00000622252.4	c.*4724G>T		3_prime_UTR_variant	Exon 12 of 12	5		ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28265 AN: 151926 Hom.: 2989 Cov.: 32

Gnomad AFR AF: 0.0981

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 8

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.186 AC: 28272 AN: 152044 Hom.: 2987 Cov.: 32 AF XY: 0.183 AC XY: 13623 AN XY: 74304

African (AFR) AF: 0.0981 AC: 4071 AN: 41484

American (AMR) AF: 0.181 AC: 2763 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 718 AN: 3470

East Asian (EAS) AF: 0.111 AC: 575 AN: 5182

South Asian (SAS) AF: 0.130 AC: 626 AN: 4814

European-Finnish (FIN) AF: 0.247 AC: 2603 AN: 10556

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16182 AN: 67954

Other (OTH) AF: 0.192 AC: 405 AN: 2112

Alfa AF: 0.223 Hom.: 6895

Bravo AF: 0.180

Asia WGS AF: 0.140 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.46
PhyloP100		-0.52
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: rs980989; hg19: chr1-232176195;