rs3802241

chr8-26765867-G-A

Variant summary

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

The ENST00000354550.4(ADRA1A):c.*184C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,403,252 control chromosomes in the GnomAD database, including 163,846 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 0.55 (24769 hom., cov: 33)
  • Exomes 𝑓: 0.46 (139077 hom.)
• Consequence: ADRA1A ENST00000354550.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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 = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1A	NM_033304.3	c.*184C>T		3_prime_UTR_variant	3/3
ADRA1A	NM_001322502.1	c.884-9088C>T		intron_variant
ADRA1A	NM_001322503.1	c.884-17119C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1A	ENST00000354550.4	c.*184C>T		3_prime_UTR_variant	3/3	1
ADRA1A	ENST00000380582.7	c.1269+4414C>T		intron_variant		1
ADRA1A	ENST00000380586.5	c.1269+4414C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83313 AN: 151976 Hom.: 24743 Cov.: 33

Gnomad AFR AF: 0.752

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.543

GnomAD4 exome AF: 0.461 AC: 577041 AN: 1251158 Hom.: 139077 Cov.: 31 AF XY: 0.462 AC XY: 278963 AN XY: 603590

Gnomad4 AFR exome AF: 0.767

Gnomad4 AMR exome AF: 0.499

Gnomad4 ASJ exome AF: 0.486

Gnomad4 EAS exome AF: 0.886

Gnomad4 SAS exome AF: 0.534

Gnomad4 FIN exome AF: 0.347

Gnomad4 NFE exome AF: 0.434

Gnomad4 OTH exome AF: 0.507

GnomAD4 genome AF: 0.548 AC: 83386 AN: 152094 Hom.: 24769 Cov.: 33 AF XY: 0.545 AC XY: 40553 AN XY: 74362

Gnomad4 AFR AF: 0.752

Gnomad4 AMR AF: 0.530

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.894

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.543

Alfa AF: 0.461 Hom.: 15480

Bravo AF: 0.569

Asia WGS AF: 0.695 AC: 2415 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	13
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3802241; hg19: chr8-26623384;