1-231672639-T-C

Variant names:

• chr1-231672639-T-C
• rs12030517
• NM_018662.3:c.68-21187T>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.68-21187T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,118 control chromosomes in the GnomAD database, including 7,682 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 0.29 (7682 hom., cov: 32)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• 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]

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 (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.68-21187T>C		intron_variant	Intron 1 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.68-21187T>C		intron_variant	Intron 1 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.68-21187T>C		intron_variant	Intron 1 of 12	5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.496-21187T>C		intron_variant	Intron 5 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44381 AN: 152000 Hom.: 7681 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.292 AC: 44381 AN: 152118 Hom.: 7682 Cov.: 32 AF XY: 0.295 AC XY: 21953 AN XY: 74342

African (AFR) AF: 0.113 AC: 4710 AN: 41532

American (AMR) AF: 0.403 AC: 6156 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1292 AN: 3470

East Asian (EAS) AF: 0.590 AC: 3037 AN: 5146

South Asian (SAS) AF: 0.326 AC: 1575 AN: 4824

European-Finnish (FIN) AF: 0.357 AC: 3772 AN: 10554

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22899 AN: 67994

Other (OTH) AF: 0.308 AC: 649 AN: 2110

Alfa AF: 0.326 Hom.: 14094

Bravo AF: 0.288

Asia WGS AF: 0.385 AC: 1340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.60
PhyloP100		-0.35
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: rs12030517; hg19: chr1-231808385;