8-26836456-G-T

Position:

• chr8-26836456-G-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+27631C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,954 control chromosomes in the GnomAD database, including 18,506 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 0.48 (18506 hom., cov: 32)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

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]

ADRA1A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA1A	NM_000680.4	c.883+27631C>A		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+27631C>A		intron_variant		2	NM_000680.4	ENSP00000369947.3

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73146 AN: 151836 Hom.: 18503 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.482 AC: 73171 AN: 151954 Hom.: 18506 Cov.: 32 AF XY: 0.476 AC XY: 35327 AN XY: 74254

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.453

Alfa AF: 0.457 Hom.: 5417

Bravo AF: 0.460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
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: rs488323; hg19: chr8-26693973;