rs486354

chr8-26852773-A-Gchr8-26852773-A-T

Variant summary

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

The NM_000680.4(ADRA1A):c.883+11314T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,104 control chromosomes in the GnomAD database, including 4,728 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 0.24 (4728 hom., cov: 33)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1A	NM_000680.4	c.883+11314T>C		intron_variant		ENST00000380573.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1A	ENST00000380573.4	c.883+11314T>C		intron_variant		2	NM_000680.4	P1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36641 AN: 151986 Hom.: 4729 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.241 AC: 36650 AN: 152104 Hom.: 4728 Cov.: 33 AF XY: 0.235 AC XY: 17491 AN XY: 74350

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.0999

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.241

Alfa AF: 0.264 Hom.: 1744

Bravo AF: 0.236

Asia WGS AF: 0.108 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.6
Dann	Benign	0.44

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: rs486354; hg19: chr8-26710290;