Variant rs12133766 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_018662.3(DISC1):c.1863G>A(p.Leu621=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 1,614,106 control chromosomes in the GnomAD database, including 2,695 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 0.046 ( 188 hom., cov: 33)

Exomes 𝑓: 0.056 ( 2507 hom. )

Consequence

DISC1
NM_018662.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.46

Variant links:

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]

DISC1 links:

DISC2 (HGNC:):

DISC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP7

Synonymous conserved (PhyloP=3.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
DISC1	NM_018662.3 linkuse as main transcript	c.1863G>A	p.Leu621=	synonymous_variant	9/13	ENST00000439617.8	NP_061132.2
DISC2	NR_002227.2 linkuse as main transcript	n.119C>T		non_coding_transcript_exon_variant	1/1
TSNAX-DISC1	NR_028393.1 linkuse as main transcript	n.2529G>A		non_coding_transcript_exon_variant	12/16
LOC105373170	XR_949268.4 linkuse as main transcript	n.296-4108C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8 linkuse as main transcript	c.1863G>A	p.Leu621=	synonymous_variant	9/13	5	NM_018662.3	ENSP00000403888	A2	Q9NRI5-1
	ENST00000651424.1 linkuse as main transcript	n.258+4326C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0458

AC:

6975

AN:

152168

Hom.:

188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0183

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0463

Gnomad ASJ

AF:

0.0919

Gnomad EAS

AF:

0.0327

Gnomad SAS

AF:

0.0518

Gnomad FIN

AF:

0.0663

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0576

Gnomad OTH

AF:

0.0527

GnomAD3 exomes

AF:

0.0502

AC:

12616

AN:

251278

Hom.:

386

AF XY:

0.0525

AC XY:

7130

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.0181

Gnomad AMR exome

AF:

0.0283

Gnomad ASJ exome

AF:

0.0833

Gnomad EAS exome

AF:

0.0293

Gnomad SAS exome

AF:

0.0457

Gnomad FIN exome

AF:

0.0577

Gnomad NFE exome

AF:

0.0613

Gnomad OTH exome

AF:

0.0577

GnomAD4 exome

AF:

0.0558

AC:

81611

AN:

1461820

Hom.:

2507

Cov.:

AF XY:

0.0563

AC XY:

40928

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0174

Gnomad4 AMR exome

AF:

0.0292

Gnomad4 ASJ exome

AF:

0.0876

Gnomad4 EAS exome

AF:

0.0231

Gnomad4 SAS exome

AF:

0.0464

Gnomad4 FIN exome

AF:

0.0543

Gnomad4 NFE exome

AF:

0.0590

Gnomad4 OTH exome

AF:

0.0587

GnomAD4 genome

AF:

0.0458

AC:

6981

AN:

152286

Hom.:

188

Cov.:

AF XY:

0.0462

AC XY:

3444

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0184

Gnomad4 AMR

AF:

0.0462

Gnomad4 ASJ

AF:

0.0919

Gnomad4 EAS

AF:

0.0328

Gnomad4 SAS

AF:

0.0520

Gnomad4 FIN

AF:

0.0663

Gnomad4 NFE

AF:

0.0576

Gnomad4 OTH

AF:

0.0521

Alfa

AF:

0.0591

Hom.:

463

Bravo

AF:

0.0436

Asia WGS

AF:

0.0400

AC:

138

AN:

3478

EpiCase

AF:

0.0667

EpiControl

AF:

0.0652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.0

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over