chr1-231697972-T-C

Variant names:

• chr1-231697972-T-C
• rs11585959
• NM_018662.3:c.1047+3167T>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.1047+3167T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,056 control chromosomes in the GnomAD database, including 6,059 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 0.28 (6059 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1047+3167T>C		intron_variant	Intron 2 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1047+3167T>C		intron_variant	Intron 2 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1047+3167T>C		intron_variant	Intron 2 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.*908+3167T>C		intron_variant	Intron 6 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41972 AN: 151938 Hom.: 6058 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.276 AC: 41986 AN: 152056 Hom.: 6059 Cov.: 31 AF XY: 0.272 AC XY: 20196 AN XY: 74324

African (AFR) AF: 0.196 AC: 8136 AN: 41476

American (AMR) AF: 0.315 AC: 4805 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1060 AN: 3472

East Asian (EAS) AF: 0.259 AC: 1338 AN: 5160

South Asian (SAS) AF: 0.221 AC: 1067 AN: 4820

European-Finnish (FIN) AF: 0.290 AC: 3067 AN: 10564

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21606 AN: 67984

Other (OTH) AF: 0.312 AC: 656 AN: 2104

Alfa AF: 0.309 Hom.: 4126

Bravo AF: 0.277

Asia WGS AF: 0.233 AC: 815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.3
DANN	Benign	0.39
PhyloP100		-0.37
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: rs11585959; hg19: chr1-231833718;