rs1383914

chr8-26865532-T-C

Variant summary

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

The NM_000680.4(ADRA1A):c.-563A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 991,098 control chromosomes in the GnomAD database, including 120,081 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 0.48 (17339 hom., cov: 31)
  • Exomes 𝑓: 0.49 (102742 hom.)
• Consequence: ADRA1A NM_000680.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1A	NM_000680.4	c.-563A>G		5_prime_UTR_variant	2/3	ENST00000380573.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1A	ENST00000380573.4	c.-563A>G		5_prime_UTR_variant	2/3	2	NM_000680.4	P1

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72311 AN: 151552 Hom.: 17329 Cov.: 31

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.460

GnomAD4 exome AF: 0.494 AC: 415074 AN: 839428 Hom.: 102742 Cov.: 36 AF XY: 0.494 AC XY: 191740 AN XY: 388010

Gnomad4 AFR exome AF: 0.453

Gnomad4 AMR exome AF: 0.457

Gnomad4 ASJ exome AF: 0.499

Gnomad4 EAS exome AF: 0.541

Gnomad4 SAS exome AF: 0.590

Gnomad4 FIN exome AF: 0.489

Gnomad4 NFE exome AF: 0.493

Gnomad4 OTH exome AF: 0.493

GnomAD4 genome AF: 0.477 AC: 72350 AN: 151670 Hom.: 17339 Cov.: 31 AF XY: 0.484 AC XY: 35832 AN XY: 74072

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.603

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.459

Alfa AF: 0.486 Hom.: 35778

Bravo AF: 0.472

Asia WGS AF: 0.554 AC: 1927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	12
Dann	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1383914; hg19: chr8-26723049;