Genetic Variant RRAD:c.*545C>T (chr16-66921531-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004165.3(RRAD):c.*545C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 152,470 control chromosomes in the GnomAD database, including 542 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.064 ( 541 hom., cov: 32)

Exomes 𝑓: 0.020 ( 1 hom. )

Consequence

RRAD
NM_004165.3 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.470

Publications

5 publications found

Variant links:

Genes affected

RRAD (HGNC:10446): (RRAD, Ras related glycolysis inhibitor and calcium channel regulator) Predicted to enable GTP binding activity and calcium channel regulator activity. Predicted to be involved in small GTPase mediated signal transduction. Predicted to be located in cytosol. Predicted to be active in plasma membrane. Implicated in type 2 diabetes mellitus. Biomarker of congestive heart failure. [provided by Alliance of Genome Resources, Apr 2022]

RRAD Gene-Disease associations (from GenCC):

Brugada syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

RRAD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004165.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRAD	NM_004165.3	MANE Select	c.*545C>T		downstream_gene	N/A	NP_004156.1	P55042
	RRAD	NM_001128850.2		c.*545C>T		downstream_gene	N/A	NP_001122322.1	P55042

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RRAD	ENST00000299759.11	TSL:1 MANE Select	c.*545C>T	downstream_gene	N/A	ENSP00000299759.6	P55042
RRAD	ENST00000889788.1		c.*545C>T	downstream_gene	N/A	ENSP00000559848.1
RRAD	ENST00000889790.1		c.*545C>T	downstream_gene	N/A	ENSP00000559849.1

Frequencies

GnomAD3 genomes

AF:

0.0643

AC:

9770

AN:

152058

Hom.:

539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.00879

Gnomad AMR

AF:

0.0387

Gnomad ASJ

AF:

0.0263

Gnomad EAS

AF:

0.0340

Gnomad SAS

AF:

0.0543

Gnomad FIN

AF:

0.0129

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0298

Gnomad OTH

AF:

0.0526

GnomAD4 exome

AF:

0.0204

AC:

AN:

294

Hom.:

AF XY:

0.0116

AC XY:

AN XY:

172

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

122

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0397

AC:

AN:

126

Other (OTH)

AF:

0.0625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0643

AC:

9787

AN:

152176

Hom.:

541

Cov.:

AF XY:

0.0625

AC XY:

4649

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.153

AC:

6369

AN:

41502

American (AMR)

AF:

0.0386

AC:

590

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0263

AC:

AN:

3466

East Asian (EAS)

AF:

0.0340

AC:

176

AN:

5170

South Asian (SAS)

AF:

0.0543

AC:

262

AN:

4822

European-Finnish (FIN)

AF:

0.0129

AC:

137

AN:

10602

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0298

AC:

2026

AN:

68002

Other (OTH)

AF:

0.0540

AC:

114

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

440

880

1319

1759

2199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0405

Hom.:

854

Bravo

AF:

0.0669

Asia WGS

AF:

0.0770

AC:

268

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.0

(source)

DANN

Benign

0.28

PhyloP100

-0.47

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over