chr1-231626905-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_018662.3(DISC1):c.38C>G(p.Ala13Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 1,502,518 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0039 ( 9 hom. )

Consequence

DISC1
NM_018662.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.23

Publications

6 publications found

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:49177): (TSNAX-DISC1 readthrough (NMD candidate)) This gene represents naturally occurring read-through transcription between the neighboring TSNAX (translin-associated factor X) and DISC1 (disrupted in schizophrenia 1) genes on chromosome 1. Alternative splicing results in multiple transcript variants, all of which are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to be protein-coding. These alterations in gene processing may be associated with risk for psychiatric illness, most notably, schizophrenia. [provided by RefSeq, Nov 2010]

TSNAX-DISC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063332915).

BP6

Variant 1-231626905-C-G is Benign according to our data. Variant chr1-231626905-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3055850.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018662.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DISC1	NM_018662.3	MANE Select	c.38C>G	p.Ala13Gly	missense	Exon 1 of 13	NP_061132.2	Q9NRI5-1
DISC1	NM_001164537.2		c.38C>G	p.Ala13Gly	missense	Exon 1 of 14	NP_001158009.1	C4P096
DISC1	NM_001012957.2		c.38C>G	p.Ala13Gly	missense	Exon 1 of 13	NP_001012975.1	Q9NRI5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DISC1	ENST00000439617.8	TSL:5 MANE Select	c.38C>G	p.Ala13Gly	missense	Exon 1 of 13	ENSP00000403888.4	Q9NRI5-1
DISC1	ENST00000366637.8	TSL:5	c.38C>G	p.Ala13Gly	missense	Exon 1 of 13	ENSP00000355597.6	Q9NRI5-2
DISC1	ENST00000366633.7	TSL:1	c.38C>G	p.Ala13Gly	missense	Exon 1 of 10	ENSP00000355593.3	Q9NRI5-5

Frequencies

GnomAD3 genomes

AF:

0.00277

AC:

420

AN:

151710

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00423

Gnomad OTH

AF:

0.00288

GnomAD2 exomes

AF:

0.00238

AC:

238

AN:

99868

AF XY:

0.00217

show subpopulations

Gnomad AFR exome

AF:

0.000484

Gnomad AMR exome

AF:

0.00123

Gnomad ASJ exome

AF:

0.00599

Gnomad EAS exome

AF:

0.000455

Gnomad FIN exome

AF:

0.000599

Gnomad NFE exome

AF:

0.00425

Gnomad OTH exome

AF:

0.000650

GnomAD4 exome

AF:

0.00387

AC:

5226

AN:

1350698

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

2474

AN XY:

666646

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

27462

American (AMR)

AF:

0.000925

AC:

AN:

30280

Ashkenazi Jewish (ASJ)

AF:

0.00531

AC:

127

AN:

23898

East Asian (EAS)

AF:

0.000121

AC:

AN:

32942

South Asian (SAS)

AF:

0.000236

AC:

AN:

76350

European-Finnish (FIN)

AF:

0.000482

AC:

AN:

33182

Middle Eastern (MID)

AF:

0.000477

AC:

AN:

4190

European-Non Finnish (NFE)

AF:

0.00457

AC:

4875

AN:

1066230

Other (OTH)

AF:

0.00223

AC:

125

AN:

56164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

276

552

827

1103

1379

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

384

576

768

960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00277

AC:

420

AN:

151820

Hom.:

Cov.:

AF XY:

0.00256

AC XY:

190

AN XY:

74182

show subpopulations

African (AFR)

AF:

0.00157

AC:

AN:

41452

American (AMR)

AF:

0.00281

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5084

South Asian (SAS)

AF:

0.000622

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000284

AC:

AN:

10548

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00423

AC:

287

AN:

67858

Other (OTH)

AF:

0.00285

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00294

Hom.:

Bravo

AF:

0.00269

ExAC

AF:

0.000748

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

DISC1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.056

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.013

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00051

LIST_S2

Benign

0.45

M_CAP

Benign

0.0018

MetaRNN

Benign

0.0063

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-1.2

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.76

REVEL

Benign

0.016

Sift

Benign

0.059

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.12

MVP

0.20

MPC

0.11

ClinPred

0.0019

GERP RS

-1.5

PromoterAI

-0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.15

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over