rs17817356

Variant names:

• chr1-231784475-G-A
• rs17817356
• NM_018662.3:c.1635-10767G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-231784475-G-A
• chr1-231784475-G-C
• chr1-231784475-G-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.1635-10767G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,978 control chromosomes in the GnomAD database, including 8,324 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 0.30 (8324 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.63
• Publications: 8 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]

ENSG00000286071 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1635-10767G>A		intron_variant	Intron 6 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1635-10767G>A		intron_variant	Intron 6 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1635-10767G>A		intron_variant	Intron 6 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.*1496-10767G>A		intron_variant	Intron 10 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45618 AN: 151858 Hom.: 8326 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.0272

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.300 AC: 45605 AN: 151978 Hom.: 8324 Cov.: 32 AF XY: 0.299 AC XY: 22209 AN XY: 74246

African (AFR) AF: 0.111 AC: 4610 AN: 41456

American (AMR) AF: 0.322 AC: 4913 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1245 AN: 3466

East Asian (EAS) AF: 0.0272 AC: 141 AN: 5180

South Asian (SAS) AF: 0.302 AC: 1452 AN: 4814

European-Finnish (FIN) AF: 0.407 AC: 4280 AN: 10510

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.411 AC: 27949 AN: 67974

Other (OTH) AF: 0.303 AC: 638 AN: 2108

Alfa AF: 0.368 Hom.: 8540

Bravo AF: 0.280

Asia WGS AF: 0.173 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.8
DANN	Benign	0.77
PhyloP100		1.6
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: rs17817356; hg19: chr1-231920221;