NM_018662.3:c.1117+17640T>C

Variant names:

• chr1-231719664-T-C
• rs1954175
• NM_018662.3:c.1117+17640T>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.1117+17640T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,186 control chromosomes in the GnomAD database, including 6,772 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 (6772 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	NM_018662.3	MANE Select	c.1117+17640T>C		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.1117+17640T>C		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.1117+17640T>C		intron	N/A	NP_001012975.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000439617.8	TSL:5 MANE Select	c.1117+17640T>C		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1117+17640T>C		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000366633.7	TSL:1	c.1117+17640T>C		intron	N/A	ENSP00000355593.3

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43224 AN: 152066 Hom.: 6768 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.284 AC: 43235 AN: 152186 Hom.: 6772 Cov.: 32 AF XY: 0.281 AC XY: 20931 AN XY: 74396

African (AFR) AF: 0.147 AC: 6100 AN: 41554

American (AMR) AF: 0.324 AC: 4953 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1071 AN: 3468

East Asian (EAS) AF: 0.373 AC: 1930 AN: 5178

South Asian (SAS) AF: 0.293 AC: 1411 AN: 4822

European-Finnish (FIN) AF: 0.316 AC: 3334 AN: 10566

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23418 AN: 67988

Other (OTH) AF: 0.335 AC: 706 AN: 2110

Alfa AF: 0.323 Hom.: 1956

Bravo AF: 0.283

Asia WGS AF: 0.335 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.85
DANN	Benign	0.72
PhyloP100		-0.48
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: rs1954175; hg19: chr1-231855410;