8-26759267-G-T

Variant names:

• chr8-26759267-G-T
• rs2036109
• ENST00000380586.5:c.1270-10519C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000380586.5(ADRA1A):​c.1270-10519C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,040 control chromosomes in the GnomAD database, including 12,125 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 0.40 (12125 hom., cov: 33)
• Consequence: ADRA1A ENST00000380586.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1A	NM_033303.4	c.1270-10519C>A		intron_variant	Intron 2 of 2		NP_150646.3
ADRA1A	NM_033302.3	c.1270-2488C>A		intron_variant	Intron 2 of 2		NP_150645.2
ADRA1A	NM_001322502.1	c.884-2488C>A		intron_variant	Intron 1 of 1		NP_001309431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA1A	ENST00000380586.5	c.1270-10519C>A		intron_variant	Intron 2 of 2	1		ENSP00000369960.1
ADRA1A	ENST00000380582.7	c.1270-2488C>A		intron_variant	Intron 2 of 2	1		ENSP00000369956.3
ADRA1A	ENST00000519096.5	n.*83-10519C>A		intron_variant	Intron 2 of 2	1		ENSP00000431073.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60297 AN: 151920 Hom.: 12121 Cov.: 33

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.397 AC: 60339 AN: 152040 Hom.: 12125 Cov.: 33 AF XY: 0.396 AC XY: 29389 AN XY: 74308

African (AFR) AF: 0.427 AC: 17719 AN: 41450

American (AMR) AF: 0.433 AC: 6618 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1490 AN: 3468

East Asian (EAS) AF: 0.511 AC: 2648 AN: 5178

South Asian (SAS) AF: 0.477 AC: 2296 AN: 4812

European-Finnish (FIN) AF: 0.282 AC: 2979 AN: 10570

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25320 AN: 67960

Other (OTH) AF: 0.409 AC: 863 AN: 2108

Alfa AF: 0.384 Hom.: 22596

Bravo AF: 0.407

Asia WGS AF: 0.495 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.40
DANN	Benign	0.45
PhyloP100		-0.33
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: rs2036109; hg19: chr8-26616784;