1-231777927-G-C

Variant names:

• chr1-231777927-G-C
• rs2812393
• NM_018662.3:c.1634+6857G>C

Variant summary

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

The ENST00000602956.5(TSNAX-DISC1):​n.*1495+6857G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,008 control chromosomes in the GnomAD database, including 28,728 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 0.61 (28728 hom., cov: 33)
• Consequence: TSNAX-DISC1 ENST00000602956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623
• 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]

ENSG00000286071 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000602956.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	NM_018662.3	MANE Select	c.1634+6857G>C		intron	N/A	NP_061132.2
	DISC1	NM_001164537.2		c.1730+6857G>C		intron	N/A	NP_001158009.1
	DISC1	NM_001012957.2		c.1634+6857G>C		intron	N/A	NP_001012975.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000439617.8	TSL:5 MANE Select	c.1634+6857G>C		intron	N/A	ENSP00000403888.4
	DISC1	ENST00000366637.8	TSL:5	c.1634+6857G>C		intron	N/A	ENSP00000355597.6
	DISC1	ENST00000366633.7	TSL:1	c.1634+6857G>C		intron	N/A	ENSP00000355593.3

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92900 AN: 151890 Hom.: 28671 Cov.: 33

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.612 AC: 93017 AN: 152008 Hom.: 28728 Cov.: 33 AF XY: 0.609 AC XY: 45243 AN XY: 74274

African (AFR) AF: 0.678 AC: 28114 AN: 41466

American (AMR) AF: 0.630 AC: 9622 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2339 AN: 3470

East Asian (EAS) AF: 0.604 AC: 3115 AN: 5156

South Asian (SAS) AF: 0.606 AC: 2919 AN: 4818

European-Finnish (FIN) AF: 0.517 AC: 5457 AN: 10550

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39322 AN: 67962

Other (OTH) AF: 0.639 AC: 1346 AN: 2106

Alfa AF: 0.595 Hom.: 3367

Bravo AF: 0.625

Asia WGS AF: 0.601 AC: 2084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-0.62
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: rs2812393; hg19: chr1-231913673;