8-26866809-C-T

Position:

• chr8-26866809-C-T

Variant summary

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

The NM_000680.4(ADRA1A):​c.-687+127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 921,656 control chromosomes in the GnomAD database, including 40,430 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 0.28 (6257 hom., cov: 31)
  • Exomes 𝑓: 0.30 (34173 hom.)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413

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=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA1A	NM_000680.4	c.-687+127G>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.-687+127G>A		intron_variant		2	NM_000680.4	ENSP00000369947	P1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42434 AN: 151822 Hom.: 6251 Cov.: 31

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.295 AC: 227283 AN: 769716 Hom.: 34173 AF XY: 0.295 AC XY: 105186 AN XY: 356700

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.331

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.385

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.301

Gnomad4 NFE exome AF: 0.292

Gnomad4 OTH exome AF: 0.304

GnomAD4 genome AF: 0.279 AC: 42459 AN: 151940 Hom.: 6257 Cov.: 31 AF XY: 0.289 AC XY: 21480 AN XY: 74274

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.275

Alfa AF: 0.291 Hom.: 13555

Bravo AF: 0.273

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.7
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3808585; hg19: chr8-26724326;