1-231683304-T-C

Variant summary

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

The NM_018662.3(DISC1):c.68-10522T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,826 control chromosomes in the GnomAD database, including 18,528 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 0.49 (18528 hom., cov: 31)
• Consequence: DISC1 NM_018662.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISC1	NM_018662.3	c.68-10522T>C		intron_variant		ENST00000439617.8
TSNAX-DISC1	NR_028393.1	n.789-10522T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISC1	ENST00000439617.8	c.68-10522T>C		intron_variant		5	NM_018662.3	A2

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73666 AN: 151708 Hom.: 18492 Cov.: 31

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.486 AC: 73759 AN: 151826 Hom.: 18528 Cov.: 31 AF XY: 0.488 AC XY: 36227 AN XY: 74190

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.548

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.488

Alfa AF: 0.433 Hom.: 17492

Bravo AF: 0.499

Asia WGS AF: 0.633 AC: 2202 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.1
Dann	Benign	0.47

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: rs1417584; hg19: chr1-231819050;