8-26847358-G-T

Variant names:

• chr8-26847358-G-T
• rs10093667
• NM_000680.4:c.883+16729C>A

Variant summary

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

The NM_000680.4(ADRA1A):​c.883+16729C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,142 control chromosomes in the GnomAD database, including 1,311 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 0.12 (1311 hom., cov: 32)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1A	NM_000680.4	c.883+16729C>A		intron_variant	Intron 2 of 2	ENST00000380573.4	NP_000671.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA1A	ENST00000380573.4	c.883+16729C>A		intron_variant	Intron 2 of 2	2	NM_000680.4	ENSP00000369947.3

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18575 AN: 152024 Hom.: 1310 Cov.: 32

Gnomad AFR AF: 0.0794

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0610

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.122 AC: 18576 AN: 152142 Hom.: 1311 Cov.: 32 AF XY: 0.122 AC XY: 9099 AN XY: 74374

African (AFR) AF: 0.0793 AC: 3291 AN: 41526

American (AMR) AF: 0.0905 AC: 1384 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3466

East Asian (EAS) AF: 0.0610 AC: 316 AN: 5182

South Asian (SAS) AF: 0.117 AC: 563 AN: 4810

European-Finnish (FIN) AF: 0.192 AC: 2028 AN: 10560

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9800 AN: 67988

Other (OTH) AF: 0.130 AC: 275 AN: 2114

Alfa AF: 0.135 Hom.: 6041

Bravo AF: 0.114

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.5
DANN	Benign	0.77
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10093667; hg19: chr8-26704875;