chr1-232008852-A-T

Variant names:

Variant summary

Our verdict is . The variant received -10 classification points (ACMG Germline Pathogenicity v2019): 0P and 10B. BA1BP4_Moderate

The NM_018662.3(DISC1):c.2110A>T (p.Ser704Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.277 (AC=447,194) in the gnomAD database across 1,611,814 control chromosomes, including 64,018 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.336. In-silico predictor (REVEL) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. This exact variant is curated in the UniProt human variants database as Uncertain Significance; it is also listed as a COSMIC curated somatic variant.

Frequency

Genomes: 𝑓 0.29 ( 6434 hom., cov: 31)

Exomes 𝑓: 0.28 ( 57584 hom. )

Consequence

DISC1
NM_018662.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.17

Publications

183 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

new If you want to explore the variant's impact on the transcript NM_018662.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -10 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Moderate).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.3365 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

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

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DISC1	NM_018662.3	MANE Select	c.2110A>T	p.Ser704Cys	missense	Exon 11 of 13	NP_061132.2	Q9NRI5-1
DISC1	NM_001164537.2		c.2206A>T	p.Ser736Cys	missense	Exon 12 of 14	NP_001158009.1	C4P096
DISC1	NM_001012957.2		c.2110A>T	p.Ser704Cys	missense	Exon 11 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.2110A>T	p.Ser704Cys	missense	Exon 11 of 13	ENSP00000403888.4	Q9NRI5-1
DISC1	ENST00000366637.8	TSL:5	c.2110A>T	p.Ser704Cys	missense	Exon 11 of 13	ENSP00000355597.6	Q9NRI5-2
DISC1	ENST00000535983.5	TSL:1	c.2049A>T	p.Arg683Ser	missense	Exon 10 of 10	ENSP00000443996.1	Q9NRI5-8

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43233

AN:

151696

Hom.:

6428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.449

Gnomad AMR

AF:

0.179

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.273

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.251

GnomAD2 exomes

AF:

0.255

AC:

62618

AN:

245122

AF XY:

0.260

show subpopulations

Gnomad AFR exome

AF:

0.343

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.115

Gnomad FIN exome

AF:

0.331

Gnomad NFE exome

AF:

0.289

Gnomad OTH exome

AF:

0.260

GnomAD4 exome

AF:

0.277

AC:

403925

AN:

1459998

Hom.:

57584

Cov.:

AF XY:

0.278

AC XY:

201633

AN XY:

726138

show subpopulations

African (AFR)

AF:

0.342

AC:

11399

AN:

33358

American (AMR)

AF:

0.129

AC:

5761

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

6212

AN:

26012

East Asian (EAS)

AF:

0.114

AC:

4525

AN:

39684

South Asian (SAS)

AF:

0.275

AC:

23693

AN:

86138

European-Finnish (FIN)

AF:

0.322

AC:

17149

AN:

53322

Middle Eastern (MID)

AF:

0.259

AC:

1489

AN:

5760

European-Non Finnish (NFE)

AF:

0.286

AC:

317631

AN:

1110866

Other (OTH)

AF:

0.267

AC:

16066

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

16397

32794

49191

65588

81985

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10370

20740

31110

41480

51850

<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:

0.285

AC:

43269

AN:

151816

Hom.:

6434

Cov.:

AF XY:

0.284

AC XY:

21066

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.332

AC:

13724

AN:

41358

American (AMR)

AF:

0.179

AC:

2731

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

849

AN:

3470

East Asian (EAS)

AF:

0.121

AC:

621

AN:

5140

South Asian (SAS)

AF:

0.275

AC:

1322

AN:

4816

European-Finnish (FIN)

AF:

0.331

AC:

3485

AN:

10514

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.287

AC:

19525

AN:

67962

Other (OTH)

AF:

0.255

AC:

537

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1523

3047

4570

6094

7617

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.277

Hom.:

4534

Bravo

AF:

0.272

Asia WGS

AF:

0.217

AC:

754

AN:

3478

EpiCase

AF:

0.281

EpiControl

AF:

0.276

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.114

AC:

13954

AN:

122722

Turkish Variome

AF:

0.286

AC:

1920

AN:

6704

Hom.:

290

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.119

AC:

1064

AN:

8960

Hom.:

ABraOM SABE-WGS-1171

AF:

0.264

AC:

618

AN:

2342

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

(source)

DANN

Uncertain

0.98

Eigen

Benign

0.11

Eigen_PC

Benign

0.0093

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.94

PhyloP100

3.2

PROVEAN

Benign

-0.34

REVEL

Benign

0.084

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.077

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over