rs3729604

Variant names:

• chr5-159917454-G-A
• rs3729604
• NM_000679.4:c.549G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-159917454-G-A
• chr5-159917454-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000679.4(ADRA1B):​c.549G>A​(p.Gly183Gly) 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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADRA1B	NM_000679.4	c.549G>A	p.Gly183Gly	synonymous_variant	Exon 1 of 2	ENST00000306675.5	NP_000670.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA1B	ENST00000306675.5	c.549G>A	p.Gly183Gly	synonymous_variant	Exon 1 of 2	1	NM_000679.4	ENSP00000306662.3
LINC01847	ENST00000641163.1	n.181+11581C>T		intron_variant	Intron 2 of 7
LINC01847	ENST00000816795.1	n.142+11581C>T		intron_variant	Intron 2 of 3

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

GnomAD2 exomes AF: 0.184 AC: 46252 AN: 251358 AF XY: 0.182

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 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

African (AFR) AF: 0.162 AC: 5439 AN: 33480

American (AMR) AF: 0.187 AC: 8345 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 3453 AN: 26136

East Asian (EAS) AF: 0.397 AC: 15774 AN: 39700

South Asian (SAS) AF: 0.151 AC: 13068 AN: 86258

European-Finnish (FIN) AF: 0.160 AC: 8522 AN: 53410

Middle Eastern (MID) AF: 0.210 AC: 1212 AN: 5768

European-Non Finnish (NFE) AF: 0.176 AC: 196111 AN: 1112004

Other (OTH) AF: 0.188 AC: 11350 AN: 60394

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

African (AFR) AF: 0.166 AC: 6882 AN: 41480

American (AMR) AF: 0.196 AC: 3001 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3470

East Asian (EAS) AF: 0.369 AC: 1897 AN: 5142

South Asian (SAS) AF: 0.147 AC: 707 AN: 4800

European-Finnish (FIN) AF: 0.162 AC: 1712 AN: 10600

Middle Eastern (MID) AF: 0.228 AC: 66 AN: 290

European-Non Finnish (NFE) AF: 0.174 AC: 11860 AN: 67984

Other (OTH) AF: 0.186 AC: 392 AN: 2106

Alfa AF: 0.180 Hom.: 11236

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
PhyloP100		-1.8
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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