rs16856202

Variant names:

• chr1-232019405-T-G
• rs16856202
• NM_018662.3:c.2308-7030T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_018662.3(DISC1):​c.2308-7030T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0326 in 152,294 control chromosomes in the GnomAD database, including 153 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 0.033 (153 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 14 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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018662.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	NM_018662.3	MANE Select	c.2308-7030T>G		intron	N/A	NP_061132.2	Q9NRI5-1
	DISC1	NM_001164537.2		c.2404-7030T>G		intron	N/A	NP_001158009.1	C4P096
	DISC1	NM_001012957.2		c.2242-7030T>G		intron	N/A	NP_001012975.1	Q9NRI5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000439617.8	TSL:5 MANE Select	c.2308-7030T>G		intron	N/A	ENSP00000403888.4	Q9NRI5-1
	DISC1	ENST00000366637.8	TSL:5	c.2242-7030T>G		intron	N/A	ENSP00000355597.6	Q9NRI5-2
	DISC1	ENST00000622252.4	TSL:5	c.*849-7030T>G		intron	N/A	ENSP00000481791.1	C4P0A0

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4964 AN: 152176 Hom.: 153 Cov.: 32

Gnomad AFR AF: 0.00820

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0290

Gnomad OTH AF: 0.0368

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

GnomAD4 genome AF: 0.0326 AC: 4964 AN: 152294 Hom.: 153 Cov.: 32 AF XY: 0.0335 AC XY: 2492 AN XY: 74476

African (AFR) AF: 0.00818 AC: 340 AN: 41570

American (AMR) AF: 0.0632 AC: 967 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3468

East Asian (EAS) AF: 0.151 AC: 783 AN: 5172

South Asian (SAS) AF: 0.0456 AC: 220 AN: 4824

European-Finnish (FIN) AF: 0.0300 AC: 319 AN: 10616

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0290 AC: 1973 AN: 68026

Other (OTH) AF: 0.0369 AC: 78 AN: 2114

Alfa AF: 0.0337 Hom.: 546

Bravo AF: 0.0351

Asia WGS AF: 0.0830 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Benign	0.69
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs16856202;

hg19: chr1-232155151;