16-90040338-C-T

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.1050C>T(p.Thr350Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0536 in 1,601,376 control chromosomes in the GnomAD database, including 2,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 145 hom., cov: 32)

Exomes 𝑓: 0.055 ( 2541 hom. )

Consequence

DRC4
NM_001481.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.60

Publications

6 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 links:

URAHP (HGNC:):

URAHP links:

URAHP (HGNC:43695): (urate (hydroxyiso-) hydrolase, pseudogene) Predicted to enable hydroxyisourate hydrolase activity. Predicted to be involved in allantoin metabolic process; purine-containing compound catabolic process; and urate catabolic process. Predicted to be active in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

URAHP 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=-0.93).

BP6

Variant 16-90040338-C-T is Benign according to our data. Variant chr16-90040338-C-T is described in ClinVar as Benign. ClinVar VariationId is 402893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.6 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DRC4	NM_001481.3 link	c.1050C>T	p.Thr350Thr	synonymous_variant	Exon 9 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.1050C>T	p.Thr350Thr	synonymous_variant	Exon 9 of 11	1	NM_001481.3	ENSP00000268699.4		O95995-1

Frequencies

GnomAD3 genomes

AF:

0.0409

AC:

6220

AN:

152184

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0133

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0187

Gnomad ASJ

AF:

0.0499

Gnomad EAS

AF:

0.0386

Gnomad SAS

AF:

0.0207

Gnomad FIN

AF:

0.0582

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0615

Gnomad OTH

AF:

0.0283

GnomAD2 exomes

AF:

0.0395

AC:

9004

AN:

228100

AF XY:

0.0397

show subpopulations

Gnomad AFR exome

AF:

0.0113

Gnomad AMR exome

AF:

0.0125

Gnomad ASJ exome

AF:

0.0474

Gnomad EAS exome

AF:

0.0337

Gnomad FIN exome

AF:

0.0597

Gnomad NFE exome

AF:

0.0552

Gnomad OTH exome

AF:

0.0364

GnomAD4 exome

AF:

0.0549

AC:

79604

AN:

1449074

Hom.:

2541

Cov.:

AF XY:

0.0539

AC XY:

38772

AN XY:

719546

show subpopulations

African (AFR)

AF:

0.0105

AC:

348

AN:

33220

American (AMR)

AF:

0.0131

AC:

565

AN:

43138

Ashkenazi Jewish (ASJ)

AF:

0.0471

AC:

1218

AN:

25852

East Asian (EAS)

AF:

0.0217

AC:

843

AN:

38930

South Asian (SAS)

AF:

0.0175

AC:

1469

AN:

84064

European-Finnish (FIN)

AF:

0.0601

AC:

3140

AN:

52246

Middle Eastern (MID)

AF:

0.00994

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.0623

AC:

68925

AN:

1106152

Other (OTH)

AF:

0.0508

AC:

3040

AN:

59840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

4444

8888

13332

17776

22220

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2532

5064

7596

10128

12660

<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:

0.0408

AC:

6217

AN:

152302

Hom.:

145

Cov.:

AF XY:

0.0399

AC XY:

2968

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0133

AC:

552

AN:

41584

American (AMR)

AF:

0.0187

AC:

286

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0499

AC:

173

AN:

3470

East Asian (EAS)

AF:

0.0387

AC:

201

AN:

5190

South Asian (SAS)

AF:

0.0207

AC:

100

AN:

4826

European-Finnish (FIN)

AF:

0.0582

AC:

618

AN:

10614

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0614

AC:

4179

AN:

68008

Other (OTH)

AF:

0.0275

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

304

608

911

1215

1519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0465

Hom.:

134

Bravo

AF:

0.0360

Asia WGS

AF:

0.0270

AC:

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

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.13

(source)

DANN

Benign

0.74

PhyloP100

-5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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