rs3739216

chr8-26769732-G-Cchr8-26769732-G-T

Variant summary

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

The NM_000680.4(ADRA1A):c.*417C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 990,204 control chromosomes in the GnomAD database, including 4,363 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 0.12 (1786 hom., cov: 32)
  • Exomes 𝑓: 0.067 (2577 hom.)
• Consequence: ADRA1A NM_000680.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

Genes affected

ADRA1A (HGNC:277): (adrenoceptor alpha 1A) 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-1A-adrenergic receptor. Alternative splicing of this gene generates four transcript variants, which encode four different isoforms with distinct C-termini but having similar ligand binding properties. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1A	NM_000680.4	c.*417C>G		3_prime_UTR_variant	3/3	ENST00000380573.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1A	ENST00000380573.4	c.*417C>G		3_prime_UTR_variant	3/3	2	NM_000680.4	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18870 AN: 152002 Hom.: 1787 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0672

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.0375

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0635

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.0670 AC: 56160 AN: 838084 Hom.: 2577 Cov.: 31 AF XY: 0.0666 AC XY: 25777 AN XY: 387162

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.0573

Gnomad4 EAS exome AF: 0.449

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.0407

Gnomad4 NFE exome AF: 0.0587

Gnomad4 OTH exome AF: 0.0989

GnomAD4 genome AF: 0.124 AC: 18886 AN: 152120 Hom.: 1786 Cov.: 32 AF XY: 0.126 AC XY: 9390 AN XY: 74400

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0672

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.0375

Gnomad4 NFE AF: 0.0635

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0404 Hom.: 34

Bravo AF: 0.136

Asia WGS AF: 0.305 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.60
Dann	Benign	0.56

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: rs3739216; hg19: chr8-26627249;