rs2793101

Variant names:

• chr1-231768532-C-T
• rs2793101
• NM_018662.3:c.1398+1263C>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.1398+1263C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 150,392 control chromosomes in the GnomAD database, including 761 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 0.098 (761 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1398+1263C>T		intron_variant	Intron 5 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1398+1263C>T		intron_variant	Intron 5 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1398+1263C>T		intron_variant	Intron 5 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.*1259+1263C>T		intron_variant	Intron 9 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.0977 AC: 14675 AN: 150274 Hom.: 761 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0554

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0247

Gnomad SAS AF: 0.0705

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.0977 AC: 14689 AN: 150392 Hom.: 761 Cov.: 32 AF XY: 0.0929 AC XY: 6816 AN XY: 73388

African (AFR) AF: 0.105 AC: 4279 AN: 40844

American (AMR) AF: 0.0554 AC: 833 AN: 15048

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 416 AN: 3430

East Asian (EAS) AF: 0.0251 AC: 129 AN: 5136

South Asian (SAS) AF: 0.0710 AC: 332 AN: 4676

European-Finnish (FIN) AF: 0.0807 AC: 848 AN: 10514

Middle Eastern (MID) AF: 0.143 AC: 41 AN: 286

European-Non Finnish (NFE) AF: 0.112 AC: 7553 AN: 67462

Other (OTH) AF: 0.105 AC: 218 AN: 2084

Alfa AF: 0.113 Hom.: 115

Bravo AF: 0.0947

Asia WGS AF: 0.0480 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.63
PhyloP100		0.32
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: rs2793101; hg19: chr1-231904278;