Variant rs3738402 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_018662.3(DISC1):c.1393C>T(p.Leu465=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 1,614,068 control chromosomes in the GnomAD database, including 3,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.051 ( 373 hom., cov: 33)

Exomes 𝑓: 0.044 ( 3012 hom. )

Consequence

DISC1
NM_018662.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.766

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:

TSNAX-DISC1 (HGNC:):

TSNAX-DISC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-231767264-C-T is Benign according to our data. Variant chr1-231767264-C-T is described in ClinVar as [Benign]. Clinvar id is 3059485.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.766 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISC1	NM_018662.3 linkuse as main transcript	c.1393C>T	p.Leu465=	synonymous_variant	5/13	ENST00000439617.8	NP_061132.2
TSNAX-DISC1	NR_028393.1 linkuse as main transcript	n.2114C>T		non_coding_transcript_exon_variant	9/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8 linkuse as main transcript	c.1393C>T	p.Leu465=	synonymous_variant	5/13	5	NM_018662.3	ENSP00000403888	A2	Q9NRI5-1

Frequencies

GnomAD3 genomes

AF:

0.0511

AC:

7779

AN:

152102

Hom.:

377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0461

Gnomad AMI

AF:

0.0921

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.0199

Gnomad EAS

AF:

0.221

Gnomad SAS

AF:

0.0836

Gnomad FIN

AF:

0.0294

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0295

Gnomad OTH

AF:

0.0589

GnomAD3 exomes

AF:

0.0756

AC:

18806

AN:

248802

Hom.:

1468

AF XY:

0.0695

AC XY:

9360

AN XY:

134698

show subpopulations

Gnomad AFR exome

AF:

0.0490

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.0215

Gnomad EAS exome

AF:

0.210

Gnomad SAS exome

AF:

0.0720

Gnomad FIN exome

AF:

0.0326

Gnomad NFE exome

AF:

0.0316

Gnomad OTH exome

AF:

0.0571

GnomAD4 exome

AF:

0.0444

AC:

64949

AN:

1461848

Hom.:

3012

Cov.:

AF XY:

0.0443

AC XY:

32204

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0487

Gnomad4 AMR exome

AF:

0.194

Gnomad4 ASJ exome

AF:

0.0203

Gnomad4 EAS exome

AF:

0.223

Gnomad4 SAS exome

AF:

0.0723

Gnomad4 FIN exome

AF:

0.0324

Gnomad4 NFE exome

AF:

0.0306

Gnomad4 OTH exome

AF:

0.0502

GnomAD4 genome

AF:

0.0510

AC:

7767

AN:

152220

Hom.:

373

Cov.:

AF XY:

0.0533

AC XY:

3968

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0459

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.0199

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.0825

Gnomad4 FIN

AF:

0.0294

Gnomad4 NFE

AF:

0.0295

Gnomad4 OTH

AF:

0.0587

Alfa

AF:

0.0388

Hom.:

279

Bravo

AF:

0.0620

Asia WGS

AF:

0.145

AC:

505

AN:

3478

EpiCase

AF:

0.0302

EpiControl

AF:

0.0294

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DISC1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.6

DANN

Benign

0.70

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over