rs3743725

Variant names:

• chr16-66921531-G-A
• rs3743725
• NM_004165.3:c.*545C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-66921531-G-A
• chr16-66921531-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.470

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RRAD	NM_004165.3	c.*545C>T		downstream_gene_variant		ENST00000299759.11	NP_004156.1
RRAD	NM_001128850.2	c.*545C>T		downstream_gene_variant			NP_001122322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RRAD	ENST00000299759.11	c.*545C>T		downstream_gene_variant		1	NM_004165.3	ENSP00000299759.6
RRAD	ENST00000568915.5	c.*219C>T		downstream_gene_variant		5		ENSP00000461995.1
RRAD	ENST00000567791.1	n.*156C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0643 AC: 9770 AN: 152058 Hom.: 539 Cov.: 32

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: 6 AN: 294 Hom.: 1 AF XY: 0.0116 AC XY: 2 AN XY: 172

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0397

Gnomad4 OTH exome AF: 0.0625

GnomAD4 genome AF: 0.0643 AC: 9787 AN: 152176 Hom.: 541 Cov.: 32 AF XY: 0.0625 AC XY: 4649 AN XY: 74412

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.0386

Gnomad4 ASJ AF: 0.0263

Gnomad4 EAS AF: 0.0340

Gnomad4 SAS AF: 0.0543

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.0298

Gnomad4 OTH AF: 0.0540

Alfa AF: 0.0351 Hom.: 228

Bravo AF: 0.0669

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3743725; hg19: chr16-66955434;