rs17178299

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001481.3(DRC4):c.776G>A(p.Arg259Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0571 in 1,611,484 control chromosomes in the GnomAD database, including 3,097 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R259W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.046 ( 216 hom., cov: 33)

Exomes 𝑓: 0.058 ( 2881 hom. )

Consequence

DRC4
NM_001481.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.70

Publications

28 publications found

Variant links:

Genes affected

DRC4 (HGNC:4166): (growth arrest specific 8) This gene includes 11 exons spanning 25 kb and maps to a region of chromosome 16 that is sometimes deleted in breast and prostrate cancer. The second intron contains an apparently intronless gene, C16orf3, that is transcribed in the opposite orientation. This gene is a putative tumor suppressor gene. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

DRC4 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 33
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DRC4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015008748).

BP6

Variant 16-90037251-G-A is Benign according to our data. Variant chr16-90037251-G-A is described in ClinVar as Benign. ClinVar VariationId is 402892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC4	NM_001481.3 link	c.776G>A	p.Arg259Gln	missense_variant	Exon 7 of 11	ENST00000268699.9	NP_001472.1	O95995-1A0A384MR00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS8	ENST00000268699.9 link	c.776G>A	p.Arg259Gln	missense_variant	Exon 7 of 11	1	NM_001481.3	ENSP00000268699.4		O95995-1

Frequencies

GnomAD3 genomes

AF:

0.0458

AC:

6962

AN:

152128

Hom.:

215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.0505

Gnomad AMR

AF:

0.0253

Gnomad ASJ

AF:

0.0507

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.0272

Gnomad FIN

AF:

0.0757

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0622

Gnomad OTH

AF:

0.0358

GnomAD2 exomes

AF:

0.0523

AC:

12981

AN:

248434

AF XY:

0.0511

show subpopulations

Gnomad AFR exome

AF:

0.00975

Gnomad AMR exome

AF:

0.0370

Gnomad ASJ exome

AF:

0.0479

Gnomad EAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.0777

Gnomad NFE exome

AF:

0.0566

Gnomad OTH exome

AF:

0.0470

GnomAD4 exome

AF:

0.0582

AC:

84987

AN:

1459238

Hom.:

2881

Cov.:

AF XY:

0.0571

AC XY:

41409

AN XY:

725666

show subpopulations

African (AFR)

AF:

0.00757

AC:

253

AN:

33406

American (AMR)

AF:

0.0337

AC:

1499

AN:

44426

Ashkenazi Jewish (ASJ)

AF:

0.0477

AC:

1241

AN:

26028

East Asian (EAS)

AF:

0.0726

AC:

2875

AN:

39618

South Asian (SAS)

AF:

0.0206

AC:

1768

AN:

85902

European-Finnish (FIN)

AF:

0.0770

AC:

4108

AN:

53356

Middle Eastern (MID)

AF:

0.0105

AC:

AN:

5440

European-Non Finnish (NFE)

AF:

0.0626

AC:

69575

AN:

1110822

Other (OTH)

AF:

0.0599

AC:

3611

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

4197

8393

12590

16786

20983

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2596

5192

7788

10384

12980

<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:

0.0457

AC:

6960

AN:

152246

Hom.:

216

Cov.:

AF XY:

0.0458

AC XY:

3408

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0109

AC:

452

AN:

41570

American (AMR)

AF:

0.0252

AC:

386

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0507

AC:

176

AN:

3470

East Asian (EAS)

AF:

0.126

AC:

652

AN:

5176

South Asian (SAS)

AF:

0.0274

AC:

132

AN:

4814

European-Finnish (FIN)

AF:

0.0757

AC:

803

AN:

10608

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0622

AC:

4232

AN:

67994

Other (OTH)

AF:

0.0364

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

332

663

995

1326

1658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0530

Hom.:

795

Bravo

AF:

0.0405

TwinsUK

AF:

0.0704

AC:

261

ALSPAC

AF:

0.0625

AC:

241

ESP6500AA

AF:

0.0114

AC:

ESP6500EA

AF:

0.0600

AC:

516

ExAC

AF:

0.0498

AC:

6042

Asia WGS

AF:

0.0760

AC:

262

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia 33

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

.;T;T

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.90

D;D;D

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-1.0

PhyloP100

5.7

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.1

N;N;.

REVEL

Benign

0.13

Sift

Uncertain

0.0090

D;D;.

Sift4G

Uncertain

0.015

D;D;D

Polyphen

0.77

.;P;.

Vest4

0.055

MPC

0.022

ClinPred

0.024

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.10

gMVP

0.22

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over