rs3729604

chr5-159917454-G-Achr5-159917454-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000679.4(ADRA1B):c.549G>A(p.Gly183=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,613,950 control chromosomes in the GnomAD database, including 27,706 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 0.18 (2549 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25157 hom.)
• Consequence: ADRA1B NM_000679.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75

Genes affected

ADRA1B (HGNC:278): (adrenoceptor alpha 1B) Alpha-1-adrenergic receptors (alpha-1-ARs) are members of the G protein-coupled receptor superfamily. They activate mitogenic responses and regulate growth and proliferation of many cells. There are 3 alpha-1-AR subtypes: alpha-1A, -1B and -1D, all of which signal through the Gq/11 family of G-proteins and different subtypes show different patterns of activation. This gene encodes alpha-1B-adrenergic receptor, which induces neoplastic transformation when transfected into NIH 3T3 fibroblasts and other cell lines. Thus, this normal cellular gene is identified as a protooncogene. This gene comprises 2 exons and a single large intron of at least 20 kb that interrupts the coding region. [provided by RefSeq, Jul 2008]

LINC01847 (HGNC:52662): (long intergenic non-protein coding RNA 1847)

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-1.75 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1B	NM_000679.4	c.549G>A	p.Gly183=	synonymous_variant	1/2	ENST00000306675.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1B	ENST00000306675.5	c.549G>A	p.Gly183=	synonymous_variant	1/2	1	NM_000679.4	P1
LINC01847	ENST00000641163.1	n.181+11581C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27197 AN: 151958 Hom.: 2549 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.183

GnomAD3 exomes AF: 0.184 AC: 46252 AN: 251358 Hom.: 4652 AF XY: 0.182 AC XY: 24767 AN XY: 135848

Gnomad AFR exome AF: 0.165

Gnomad AMR exome AF: 0.185

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.359

Gnomad SAS exome AF: 0.154

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.180 AC: 263274 AN: 1461874 Hom.: 25157 Cov.: 33 AF XY: 0.179 AC XY: 130093 AN XY: 727238

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.179 AC: 27229 AN: 152076 Hom.: 2549 Cov.: 32 AF XY: 0.180 AC XY: 13405 AN XY: 74336

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.186

Alfa AF: 0.180 Hom.: 5178

Bravo AF: 0.182

Asia WGS AF: 0.256 AC: 891 AN: 3478

EpiCase AF: 0.179

EpiControl AF: 0.186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	2.2
Dann	Benign	0.67

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

LitVar

Other links and lift over

dbSNP: rs3729604; hg19: chr5-159344461; COSMIC: COSV60700916; COSMIC: COSV60700916;