rs486179

chr8-26866417-T-Cchr8-26866417-T-G

Variant summary

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

The NM_000680.4(ADRA1A):c.-687+519A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,182 control chromosomes in the GnomAD database, including 59,572 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 0.88 (59572 hom., cov: 31)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1A	NM_000680.4	c.-687+519A>G		intron_variant		ENST00000380573.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1A	ENST00000380573.4	c.-687+519A>G		intron_variant		2	NM_000680.4	P1

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133546 AN: 152064 Hom.: 59542 Cov.: 31

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.987

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.887

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

GnomAD4 genome AF: 0.878 AC: 133629 AN: 152182 Hom.: 59572 Cov.: 31 AF XY: 0.879 AC XY: 65414 AN XY: 74386

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.878

Gnomad4 ASJ AF: 0.987

Gnomad4 EAS AF: 0.909

Gnomad4 SAS AF: 0.933

Gnomad4 FIN AF: 0.942

Gnomad4 NFE AF: 0.955

Gnomad4 OTH AF: 0.883

Alfa AF: 0.933 Hom.: 26861

Bravo AF: 0.866

Asia WGS AF: 0.890 AC: 3097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	13
Dann	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs486179; hg19: chr8-26723934;