rs574647

Variant names:

• chr8-26839540-T-C
• rs574647
• NM_000680.4:c.883+24547A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000680.4(ADRA1A):​c.883+24547A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,052 control chromosomes in the GnomAD database, including 38,031 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 0.70 (38031 hom., cov: 31)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1A	NM_000680.4	c.883+24547A>G		intron_variant	Intron 2 of 2	ENST00000380573.4	NP_000671.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA1A	ENST00000380573.4	c.883+24547A>G		intron_variant	Intron 2 of 2	2	NM_000680.4	ENSP00000369947.3

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107044 AN: 151934 Hom.: 38021 Cov.: 31

Gnomad AFR AF: 0.735

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.704 AC: 107100 AN: 152052 Hom.: 38031 Cov.: 31 AF XY: 0.701 AC XY: 52102 AN XY: 74312

African (AFR) AF: 0.735 AC: 30463 AN: 41470

American (AMR) AF: 0.557 AC: 8513 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2529 AN: 3468

East Asian (EAS) AF: 0.550 AC: 2836 AN: 5156

South Asian (SAS) AF: 0.605 AC: 2918 AN: 4824

European-Finnish (FIN) AF: 0.758 AC: 8006 AN: 10568

Middle Eastern (MID) AF: 0.702 AC: 205 AN: 292

European-Non Finnish (NFE) AF: 0.727 AC: 49437 AN: 67974

Other (OTH) AF: 0.690 AC: 1460 AN: 2116

Alfa AF: 0.707 Hom.: 73249

Bravo AF: 0.688

Asia WGS AF: 0.572 AC: 1993 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	1.3
DANN	Benign	0.43
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs574647; hg19: chr8-26697057;