rs10102186

Positions:

• chr8-26767134-G-A
• chr8-26767134-G-C

Variant summary

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

The ENST00000380586.5(ADRA1A):​c.1269+3147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,942 control chromosomes in the GnomAD database, including 7,149 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 0.30 (7149 hom., cov: 32)
• Consequence: ADRA1A ENST00000380586.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1A	NM_001322502.1	c.884-10355C>T		intron_variant
ADRA1A	NM_001322503.1	c.884-18386C>T		intron_variant
ADRA1A	NM_033302.3	c.1269+3147C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1A	ENST00000354550.4	c.1270-985C>T		intron_variant		1
ADRA1A	ENST00000380582.7	c.1269+3147C>T		intron_variant		1
ADRA1A	ENST00000380586.5	c.1269+3147C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46057 AN: 151824 Hom.: 7142 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.0667

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.303 AC: 46090 AN: 151942 Hom.: 7149 Cov.: 32 AF XY: 0.300 AC XY: 22271 AN XY: 74264

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.0667

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.320

Alfa AF: 0.291 Hom.: 3920

Bravo AF: 0.304

Asia WGS AF: 0.199 AC: 694 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.56
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10102186; hg19: chr8-26624651;