Variant 1-231866586-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001012959.2(DISC1):c.*8C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0505 in 1,370,204 control chromosomes in the GnomAD database, including 1,995 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.041 ( 158 hom., cov: 32)

Exomes 𝑓: 0.052 ( 1837 hom. )

Consequence

DISC1
NM_001012959.2 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.296

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:

DISC1 (HGNC:):

DISC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-231866586-C-G is Benign according to our data. Variant chr1-231866586-C-G is described in ClinVar as [Benign]. Clinvar id is 3060171.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0609 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.1981+48069C>G		intron_variant		ENST00000439617.8	NP_061132.2	Q9NRI5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8 linkuse as main transcript	c.1981+48069C>G		intron_variant		5	NM_018662.3	ENSP00000403888.4		Q9NRI5-1
DISC1	ENST00000366637.8 linkuse as main transcript	c.1981+48069C>G		intron_variant		5		ENSP00000355597.6		Q9NRI5-2

Frequencies

GnomAD3 genomes

AF:

0.0407

AC:

6194

AN:

152128

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0403

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.0666

Gnomad SAS

AF:

0.0636

Gnomad FIN

AF:

0.0455

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0510

Gnomad OTH

AF:

0.0506

GnomAD3 exomes

AF:

0.0488

AC:

12126

AN:

248290

Hom.:

361

AF XY:

0.0521

AC XY:

7005

AN XY:

134380

show subpopulations

Gnomad AFR exome

AF:

0.0110

Gnomad AMR exome

AF:

0.0267

Gnomad ASJ exome

AF:

0.0900

Gnomad EAS exome

AF:

0.0653

Gnomad SAS exome

AF:

0.0627

Gnomad FIN exome

AF:

0.0378

Gnomad NFE exome

AF:

0.0528

Gnomad OTH exome

AF:

0.0559

GnomAD4 exome

AF:

0.0518

AC:

63043

AN:

1217958

Hom.:

1837

Cov.:

AF XY:

0.0529

AC XY:

32713

AN XY:

618238

show subpopulations

Gnomad4 AFR exome

AF:

0.0106

Gnomad4 AMR exome

AF:

0.0273

Gnomad4 ASJ exome

AF:

0.0940

Gnomad4 EAS exome

AF:

0.0560

Gnomad4 SAS exome

AF:

0.0621

Gnomad4 FIN exome

AF:

0.0351

Gnomad4 NFE exome

AF:

0.0525

Gnomad4 OTH exome

AF:

0.0581

GnomAD4 genome

AF:

0.0407

AC:

6197

AN:

152246

Hom.:

158

Cov.:

AF XY:

0.0407

AC XY:

3028

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0116

Gnomad4 AMR

AF:

0.0403

Gnomad4 ASJ

AF:

0.103

Gnomad4 EAS

AF:

0.0667

Gnomad4 SAS

AF:

0.0638

Gnomad4 FIN

AF:

0.0455

Gnomad4 NFE

AF:

0.0510

Gnomad4 OTH

AF:

0.0501

Alfa

AF:

0.0531

Hom.:

Bravo

AF:

0.0382

Asia WGS

AF:

0.0570

AC:

198

AN:

3478

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

Jun 13, 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

-0.82

CADD

Benign

5.3

DANN

Benign

0.53

Splicing

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