NM_001481.3:c.597A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001481.3(DRC4):c.597A>G(p.Glu199Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,611,578 control chromosomes in the GnomAD database, including 125,276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10512 hom., cov: 33)

Exomes 𝑓: 0.39 ( 114764 hom. )

Consequence

DRC4
NM_001481.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.00

Publications

29 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 16-90036427-A-G is Benign according to our data. Variant chr16-90036427-A-G is described in ClinVar as [Benign]. Clinvar id is 402891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC4	NM_001481.3 link	c.597A>G	p.Glu199Glu	synonymous_variant	Exon 6 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.597A>G	p.Glu199Glu	synonymous_variant	Exon 6 of 11	1	NM_001481.3	ENSP00000268699.4		O95995-1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54756

AN:

152016

Hom.:

10501

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.419

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.499

Gnomad EAS

AF:

0.0154

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.399

Gnomad OTH

AF:

0.374

GnomAD2 exomes

AF:

0.320

AC:

80201

AN:

250594

AF XY:

0.325

show subpopulations

Gnomad AFR exome

AF:

0.384

Gnomad AMR exome

AF:

0.209

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.00832

Gnomad FIN exome

AF:

0.288

Gnomad NFE exome

AF:

0.396

Gnomad OTH exome

AF:

0.351

GnomAD4 exome

AF:

0.386

AC:

563155

AN:

1459444

Hom.:

114764

Cov.:

AF XY:

0.384

AC XY:

278481

AN XY:

725566

show subpopulations

African (AFR)

AF:

0.373

AC:

12465

AN:

33400

American (AMR)

AF:

0.219

AC:

9744

AN:

44558

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

13060

AN:

26098

East Asian (EAS)

AF:

0.0148

AC:

587

AN:

39652

South Asian (SAS)

AF:

0.278

AC:

23967

AN:

86110

European-Finnish (FIN)

AF:

0.287

AC:

15322

AN:

53398

Middle Eastern (MID)

AF:

0.405

AC:

2331

AN:

5762

European-Non Finnish (NFE)

AF:

0.417

AC:

463063

AN:

1110180

Other (OTH)

AF:

0.375

AC:

22616

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

17234

34469

51703

68938

86172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14088

28176

42264

56352

70440

<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:

0.360

AC:

54803

AN:

152134

Hom.:

10512

Cov.:

AF XY:

0.350

AC XY:

26060

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.384

AC:

15903

AN:

41450

American (AMR)

AF:

0.286

AC:

4376

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.499

AC:

1734

AN:

3472

East Asian (EAS)

AF:

0.0154

AC:

AN:

5186

South Asian (SAS)

AF:

0.266

AC:

1281

AN:

4822

European-Finnish (FIN)

AF:

0.284

AC:

3006

AN:

10600

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.399

AC:

27129

AN:

67998

Other (OTH)

AF:

0.371

AC:

783

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1800

3601

5401

7202

9002

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.391

Hom.:

48995

Bravo

AF:

0.364

Asia WGS

AF:

0.157

AC:

547

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 33

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.6

(source)

DANN

Benign

0.52

PhyloP100

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

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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