rs573514

Positions:

• chr8-26863764-A-G
• chr8-26863764-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+323T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,070 control chromosomes in the GnomAD database, including 10,150 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 0.36 (10150 hom., cov: 32)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.638

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA1A	NM_000680.4	c.883+323T>C		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+323T>C		intron_variant		2	NM_000680.4	ENSP00000369947	P1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54457 AN: 151952 Hom.: 10142 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.358 AC: 54499 AN: 152070 Hom.: 10150 Cov.: 32 AF XY: 0.353 AC XY: 26251 AN XY: 74326

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.454

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.383

Alfa AF: 0.400 Hom.: 13265

Bravo AF: 0.356

Asia WGS AF: 0.323 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.5
DANN	Benign	0.61

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: rs573514; hg19: chr8-26721281;