chr1-231633700-T-A

Variant names:

• chr1-231633700-T-A
• rs823165
• NM_018662.3:c.67+6766T>A

Variant summary

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

The NM_018662.3(DISC1):​c.67+6766T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,984 control chromosomes in the GnomAD database, including 10,897 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 0.37 (10897 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.67+6766T>A		intron_variant	Intron 1 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.67+6766T>A		intron_variant	Intron 1 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.67+6766T>A		intron_variant	Intron 1 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.496-60126T>A		intron_variant	Intron 5 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55612 AN: 151866 Hom.: 10882 Cov.: 31

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.366 AC: 55662 AN: 151984 Hom.: 10897 Cov.: 31 AF XY: 0.371 AC XY: 27596 AN XY: 74292

African (AFR) AF: 0.333 AC: 13811 AN: 41454

American (AMR) AF: 0.444 AC: 6772 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1327 AN: 3470

East Asian (EAS) AF: 0.808 AC: 4177 AN: 5170

South Asian (SAS) AF: 0.413 AC: 1993 AN: 4820

European-Finnish (FIN) AF: 0.371 AC: 3911 AN: 10538

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22606 AN: 67964

Other (OTH) AF: 0.364 AC: 770 AN: 2114

Alfa AF: 0.345 Hom.: 1136

Bravo AF: 0.373

Asia WGS AF: 0.553 AC: 1923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.4
DANN	Benign	0.73
PhyloP100		0.33
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: rs823165; hg19: chr1-231769446;