chr1-232037775-C-T

Variant names:

• chr1-232037775-C-T
• rs11578905
• NM_018662.3:c.*944C>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.*944C>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 0.236 in 150,636 control chromosomes in the GnomAD database, including 4,318 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 0.24 (4316 hom., cov: 31)
  • Exomes 𝑓: 0.19 (2 hom.)
• Consequence: DISC1 NM_018662.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918
• Publications: 4 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 (NFE) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018662.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	NM_018662.3	MANE Select	c.*944C>T		3_prime_UTR	Exon 13 of 13	NP_061132.2
	DISC1	NM_001164537.2		c.*944C>T		3_prime_UTR	Exon 14 of 14	NP_001158009.1
	DISC1	NM_001012957.2		c.*944C>T		3_prime_UTR	Exon 13 of 13	NP_001012975.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000439617.8	TSL:5 MANE Select	c.*944C>T		3_prime_UTR	Exon 13 of 13	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.*944C>T		3_prime_UTR	Exon 13 of 13	ENSP00000355597.6
	DISC1	ENST00000622252.4	TSL:5	c.*2050C>T		3_prime_UTR	Exon 12 of 12	ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35451 AN: 150426 Hom.: 4315 Cov.: 31

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.267

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.188 AC: 18 AN: 96 Hom.: 2 Cov.: 0 AF XY: 0.200 AC XY: 12 AN XY: 60

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.167 AC: 1 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.179 AC: 14 AN: 78

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.236 AC: 35469 AN: 150540 Hom.: 4316 Cov.: 31 AF XY: 0.234 AC XY: 17152 AN XY: 73456

African (AFR) AF: 0.201 AC: 8197 AN: 40868

American (AMR) AF: 0.220 AC: 3329 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 746 AN: 3452

East Asian (EAS) AF: 0.171 AC: 860 AN: 5018

South Asian (SAS) AF: 0.184 AC: 862 AN: 4674

European-Finnish (FIN) AF: 0.287 AC: 2974 AN: 10356

Middle Eastern (MID) AF: 0.266 AC: 73 AN: 274

European-Non Finnish (NFE) AF: 0.260 AC: 17596 AN: 67772

Other (OTH) AF: 0.228 AC: 475 AN: 2086

Alfa AF: 0.236 Hom.: 884

Bravo AF: 0.230

Asia WGS AF: 0.192 AC: 669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.28
DANN	Benign	0.23
PhyloP100		-0.92
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: rs11578905; hg19: chr1-232173521;