rs16856199

Variant names:

• chr1-232018366-T-A
• rs16856199
• NM_018662.3:c.2308-8069T>A

Variant summary

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

The NM_018662.3(DISC1):​c.2308-8069T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0977 in 152,238 control chromosomes in the GnomAD database, including 1,853 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 0.098 (1853 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.2308-8069T>A		intron_variant	Intron 11 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.2308-8069T>A		intron_variant	Intron 11 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.2242-8069T>A		intron_variant	Intron 11 of 12	5		ENSP00000355597.6
DISC1	ENST00000622252.4	c.*849-8069T>A		intron_variant	Intron 10 of 11	5		ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.0976 AC: 14849 AN: 152120 Hom.: 1849 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.00960

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0232

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0977 AC: 14880 AN: 152238 Hom.: 1853 Cov.: 32 AF XY: 0.0948 AC XY: 7055 AN XY: 74448

African (AFR) AF: 0.290 AC: 12046 AN: 41502

American (AMR) AF: 0.0493 AC: 755 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 151 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4830

European-Finnish (FIN) AF: 0.00960 AC: 102 AN: 10620

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0232 AC: 1576 AN: 68012

Other (OTH) AF: 0.0747 AC: 158 AN: 2114

Alfa AF: 0.0687 Hom.: 145

Bravo AF: 0.108

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.67
PhyloP100		-0.047
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16856199; hg19: chr1-232154112;