Variant rs6675281 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018662.3(DISC1):c.1819C>T(p.Leu607Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,613,712 control chromosomes in the GnomAD database, including 15,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.14 ( 1709 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13418 hom. )

Consequence

DISC1
NM_018662.3 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 3.36

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001408428).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 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.1819C>T	p.Leu607Phe	missense_variant	9/13	ENST00000439617.8	NP_061132.2
DISC2	NR_002227.2 linkuse as main transcript	n.163G>A		non_coding_transcript_exon_variant	1/1
TSNAX-DISC1	NR_028393.1 linkuse as main transcript	n.2485C>T		non_coding_transcript_exon_variant	12/16
LOC105373170	XR_949268.4 linkuse as main transcript	n.296-4064G>A		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.1819C>T	p.Leu607Phe	missense_variant	9/13	5	NM_018662.3	ENSP00000403888	A2	Q9NRI5-1
	ENST00000651424.1 linkuse as main transcript	n.258+4370G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21126

AN:

152032

Hom.:

1702

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.244

Gnomad AMR

AF:

0.0811

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.00424

Gnomad SAS

AF:

0.0483

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.111

AC:

27823

AN:

251170

Hom.:

1953

AF XY:

0.110

AC XY:

14955

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.175

Gnomad AMR exome

AF:

0.0537

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.00310

Gnomad SAS exome

AF:

0.0542

Gnomad FIN exome

AF:

0.154

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.129

AC:

189219

AN:

1461562

Hom.:

13418

Cov.:

AF XY:

0.127

AC XY:

92445

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.181

Gnomad4 AMR exome

AF:

0.0577

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.00169

Gnomad4 SAS exome

AF:

0.0565

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.139

AC:

21147

AN:

152150

Hom.:

1709

Cov.:

AF XY:

0.135

AC XY:

10077

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.180

Gnomad4 AMR

AF:

0.0810

Gnomad4 ASJ

AF:

0.117

Gnomad4 EAS

AF:

0.00425

Gnomad4 SAS

AF:

0.0483

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.134

Hom.:

3502

Bravo

AF:

0.137

TwinsUK

AF:

0.135

AC:

500

ALSPAC

AF:

0.133

AC:

513

ESP6500AA

AF:

0.177

AC:

781

ESP6500EA

AF:

0.142

AC:

1218

ExAC

AF:

0.116

AC:

14028

Asia WGS

AF:

0.0460

AC:

164

AN:

3478

EpiCase

AF:

0.137

EpiControl

AF:

0.129

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

not provided, no classification provided

literature only

Psychiatry Genetics Yale University

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

.;.;.;.;.;T;D

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.89

D;D;D;D;D;D;D

MetaRNN

Benign

0.0014

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.045

P;P;P;P;P;P;P;P;P

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.9

.;D;D;D;D;.;D

REVEL

Benign

0.17

Sift

Pathogenic

0.0

.;.;D;D;D;.;D

Sift4G

Uncertain

0.013

D;D;D;D;D;D;D

Polyphen

1.0, 0.99

.;.;D;.;D;.;D

Vest4

0.44

MPC

0.56

ClinPred

0.030

GERP RS

4.3

Varity_R

0.099

gMVP

0.30

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