chr1-231967601-C-T

Variant names:

• chr1-231967601-C-T
• rs821598
• NM_018662.3:c.2042+8713C>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.2042+8713C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,966 control chromosomes in the GnomAD database, including 8,977 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 0.33 (8977 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 1 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 (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.2042+8713C>T		intron_variant	Intron 10 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.2042+8713C>T		intron_variant	Intron 10 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.2042+8713C>T		intron_variant	Intron 10 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50532 AN: 151846 Hom.: 8965 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.333 AC: 50585 AN: 151966 Hom.: 8977 Cov.: 32 AF XY: 0.333 AC XY: 24729 AN XY: 74272

African (AFR) AF: 0.444 AC: 18408 AN: 41424

American (AMR) AF: 0.210 AC: 3203 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 976 AN: 3470

East Asian (EAS) AF: 0.172 AC: 892 AN: 5182

South Asian (SAS) AF: 0.375 AC: 1805 AN: 4814

European-Finnish (FIN) AF: 0.346 AC: 3635 AN: 10520

Middle Eastern (MID) AF: 0.259 AC: 75 AN: 290

European-Non Finnish (NFE) AF: 0.302 AC: 20527 AN: 67980

Other (OTH) AF: 0.300 AC: 632 AN: 2110

Alfa AF: 0.321 Hom.: 1549

Bravo AF: 0.321

Asia WGS AF: 0.320 AC: 1112 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.67
DANN	Benign	0.44
PhyloP100		-0.21
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: rs821598; hg19: chr1-232103347; COSMIC: COSV64093667;