1-231818681-C-T

Position:

• chr1-231818681-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164544.2(DISC1):​c.*156C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 1,437,096 control chromosomes in the GnomAD database, including 334,882 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 0.66 (33419 hom., cov: 33)
  • Exomes 𝑓: 0.68 (301463 hom.)
• Consequence: DISC1 NM_001164544.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1981+164C>T		intron_variant		ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.1981+164C>T		intron_variant		5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1981+164C>T		intron_variant		5		ENSP00000355597.6
TSNAX-DISC1	ENST00000602956.5	n.*2006C>T		non_coding_transcript_exon_variant	13/13	2		ENSP00000473532.1
TSNAX-DISC1	ENST00000602956.5	n.*2006C>T		3_prime_UTR_variant	13/13	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100209 AN: 151876 Hom.: 33396 Cov.: 33

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.673

GnomAD4 exome AF: 0.684 AC: 879237 AN: 1285102 Hom.: 301463 Cov.: 41 AF XY: 0.684 AC XY: 426146 AN XY: 622704

Gnomad4 AFR exome AF: 0.567

Gnomad4 AMR exome AF: 0.763

Gnomad4 ASJ exome AF: 0.676

Gnomad4 EAS exome AF: 0.780

Gnomad4 SAS exome AF: 0.676

Gnomad4 FIN exome AF: 0.710

Gnomad4 NFE exome AF: 0.683

Gnomad4 OTH exome AF: 0.677

GnomAD4 genome AF: 0.660 AC: 100279 AN: 151994 Hom.: 33419 Cov.: 33 AF XY: 0.664 AC XY: 49307 AN XY: 74298

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.676

Alfa AF: 0.673 Hom.: 57317

Bravo AF: 0.657

Asia WGS AF: 0.723 AC: 2513 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	6.8
DANN	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs1535530; hg19: chr1-231954427;