rs10495310

Positions:

• chr1-231783030-A-C

Variant summary

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

The NM_018662.3(DISC1):​c.1634+11960A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,152 control chromosomes in the GnomAD database, including 1,963 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 0.15 (1963 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.445

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1634+11960A>C		intron_variant		ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1634+11960A>C		intron_variant		5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1634+11960A>C		intron_variant		5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.*1495+11960A>C		intron_variant		2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22382 AN: 152034 Hom.: 1965 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.147 AC: 22409 AN: 152152 Hom.: 1963 Cov.: 32 AF XY: 0.147 AC XY: 10898 AN XY: 74388

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.0588

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.174

Alfa AF: 0.122 Hom.: 1045

Bravo AF: 0.160

Asia WGS AF: 0.194 AC: 674 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	5.7
DANN	Benign	0.67

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: rs10495310; hg19: chr1-231918776;