rs9659649

Variant names:

• chr1-231891762-T-A
• rs9659649
• NM_018662.3:c.1982-67066T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-231891762-T-A
• chr1-231891762-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018662.3(DISC1):​c.1982-67066T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 151,858 control chromosomes in the GnomAD database, including 31,811 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 0.64 (31811 hom., cov: 30)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.37
• Publications: 2 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=-1.06).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1982-67066T>A		intron_variant	Intron 9 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1982-67066T>A		intron_variant	Intron 9 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1982-67066T>A		intron_variant	Intron 9 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97802 AN: 151740 Hom.: 31788 Cov.: 30

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.644 AC: 97871 AN: 151858 Hom.: 31811 Cov.: 30 AF XY: 0.642 AC XY: 47610 AN XY: 74212

African (AFR) AF: 0.622 AC: 25762 AN: 41390

American (AMR) AF: 0.691 AC: 10557 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2249 AN: 3468

East Asian (EAS) AF: 0.468 AC: 2406 AN: 5138

South Asian (SAS) AF: 0.604 AC: 2905 AN: 4806

European-Finnish (FIN) AF: 0.624 AC: 6584 AN: 10546

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45339 AN: 67928

Other (OTH) AF: 0.659 AC: 1391 AN: 2110

Alfa AF: 0.647 Hom.: 3770

Bravo AF: 0.648

Asia WGS AF: 0.529 AC: 1843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.20
DANN	Benign	0.37
PhyloP100		-3.4
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: rs9659649; hg19: chr1-232027508;