chr8-26767134-G-A

Variant names:

• chr8-26767134-G-A
• rs10102186
• ENST00000380586.5:c.1269+3147C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000380586.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1A	NM_033303.4		c.1269+3147C>T		intron	N/A	NP_150646.3
	ADRA1A	NM_033304.3		c.1270-985C>T		intron	N/A	NP_150647.2
	ADRA1A	NM_033302.3		c.1269+3147C>T		intron	N/A	NP_150645.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1A	ENST00000380586.5	TSL:1	c.1269+3147C>T		intron	N/A	ENSP00000369960.1
	ADRA1A	ENST00000354550.4	TSL:1	c.1270-985C>T		intron	N/A	ENSP00000346557.4
	ADRA1A	ENST00000380582.7	TSL:1	c.1269+3147C>T		intron	N/A	ENSP00000369956.3

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

African (AFR) AF: 0.331 AC: 13701 AN: 41428

American (AMR) AF: 0.289 AC: 4411 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1307 AN: 3470

East Asian (EAS) AF: 0.0667 AC: 345 AN: 5172

South Asian (SAS) AF: 0.287 AC: 1382 AN: 4814

European-Finnish (FIN) AF: 0.257 AC: 2709 AN: 10540

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21227 AN: 67942

Other (OTH) AF: 0.320 AC: 673 AN: 2106

Alfa AF: 0.296 Hom.: 6422

Bravo AF: 0.304

Asia WGS AF: 0.199 AC: 694 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.56
DANN	Benign	0.44
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10102186; hg19: chr8-26624651;