rs10495310

Variant names:

• chr1-231783030-A-C
• rs10495310
• NM_018662.3:c.1634+11960A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1634+11960A>C		intron_variant	Intron 6 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1634+11960A>C		intron_variant	Intron 6 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1634+11960A>C		intron_variant	Intron 6 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.*1495+11960A>C		intron_variant	Intron 10 of 12	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

African (AFR) AF: 0.219 AC: 9068 AN: 41480

American (AMR) AF: 0.162 AC: 2482 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3466

East Asian (EAS) AF: 0.191 AC: 987 AN: 5174

South Asian (SAS) AF: 0.213 AC: 1025 AN: 4820

European-Finnish (FIN) AF: 0.0588 AC: 624 AN: 10608

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7233 AN: 68006

Other (OTH) AF: 0.174 AC: 368 AN: 2110

Alfa AF: 0.121 Hom.: 1416

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
PhyloP100		0.45
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: rs10495310; hg19: chr1-231918776;