rs6541281

Positions:

• chr1-231677388-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018662.3(DISC1):​c.68-16438C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,078 control chromosomes in the GnomAD database, including 12,893 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 0.40 (12893 hom., cov: 33)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.251

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]

DISC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.68-16438C>T		intron_variant		ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.68-16438C>T		intron_variant		5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.68-16438C>T		intron_variant		5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.496-16438C>T		intron_variant		2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60353 AN: 151960 Hom.: 12896 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.397 AC: 60345 AN: 152078 Hom.: 12893 Cov.: 33 AF XY: 0.401 AC XY: 29786 AN XY: 74354

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.405

Alfa AF: 0.458 Hom.: 22283

Bravo AF: 0.378

Asia WGS AF: 0.314 AC: 1091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.64
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs6541281; hg19: chr1-231813134;