rs1079078

Positions:

• chr8-26840530-A-C
• chr8-26840530-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+23557T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,048 control chromosomes in the GnomAD database, including 2,895 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 0.19 (2895 hom., cov: 32)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA1A	NM_000680.4	c.883+23557T>G		intron_variant		ENST00000380573.4	NP_000671.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA1A	ENST00000380573.4	c.883+23557T>G		intron_variant		2	NM_000680.4	ENSP00000369947	P1

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28782 AN: 151940 Hom.: 2895 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.189 AC: 28802 AN: 152048 Hom.: 2895 Cov.: 32 AF XY: 0.195 AC XY: 14496 AN XY: 74292

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.187

Alfa AF: 0.185 Hom.: 2822

Bravo AF: 0.181

Asia WGS AF: 0.333 AC: 1157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.3
DANN	Benign	0.57

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: rs1079078; hg19: chr8-26698047;