chr1-231871473-T-C

Variant names:

• chr1-231871473-T-C
• rs9432024
• NM_018662.3:c.1981+52956T>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.1981+52956T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,020 control chromosomes in the GnomAD database, including 11,335 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 0.38 (11335 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1981+52956T>C		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.1981+52956T>C		intron_variant	Intron 9 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1981+52956T>C		intron_variant	Intron 9 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57357 AN: 151902 Hom.: 11319 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.378 AC: 57411 AN: 152020 Hom.: 11335 Cov.: 32 AF XY: 0.374 AC XY: 27773 AN XY: 74300

African (AFR) AF: 0.492 AC: 20387 AN: 41408

American (AMR) AF: 0.365 AC: 5581 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1392 AN: 3466

East Asian (EAS) AF: 0.166 AC: 859 AN: 5164

South Asian (SAS) AF: 0.320 AC: 1540 AN: 4818

European-Finnish (FIN) AF: 0.296 AC: 3135 AN: 10576

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23278 AN: 67984

Other (OTH) AF: 0.360 AC: 760 AN: 2112

Alfa AF: 0.352 Hom.: 25051

Bravo AF: 0.386

Asia WGS AF: 0.233 AC: 810 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.19
PhyloP100		-0.60
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: rs9432024; hg19: chr1-232007219;