rs17426222

Positions:

• chr8-26860300-C-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+3787G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,026 control chromosomes in the GnomAD database, including 3,840 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 0.21 (3840 hom., cov: 31)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1A	NM_000680.4	c.883+3787G>A		intron_variant		ENST00000380573.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1A	ENST00000380573.4	c.883+3787G>A		intron_variant		2	NM_000680.4	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31357 AN: 151908 Hom.: 3839 Cov.: 31

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.206 AC: 31352 AN: 152026 Hom.: 3840 Cov.: 31 AF XY: 0.206 AC XY: 15275 AN XY: 74312

Gnomad4 AFR AF: 0.0830

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.210

Alfa AF: 0.251 Hom.: 6709

Bravo AF: 0.189

Asia WGS AF: 0.195 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.6
DANN	Benign	0.52

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: rs17426222; hg19: chr8-26717817;