rs520180

Variant names:

• chr8-26852405-G-A
• rs520180
• NM_000680.4:c.883+11682C>T

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+11682C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 151,918 control chromosomes in the GnomAD database, including 38,154 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 0.71 (38154 hom., cov: 33)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.483
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000680.4. 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_000680.4	MANE Select	c.883+11682C>T		intron	N/A	NP_000671.2
	ADRA1A	NM_033303.4		c.883+11682C>T		intron	N/A	NP_150646.3
	ADRA1A	NM_033304.3		c.883+11682C>T		intron	N/A	NP_150647.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1A	ENST00000380573.4	TSL:2 MANE Select	c.883+11682C>T		intron	N/A	ENSP00000369947.3
	ADRA1A	ENST00000380586.5	TSL:1	c.883+11682C>T		intron	N/A	ENSP00000369960.1
	ADRA1A	ENST00000276393.8	TSL:1	c.883+11682C>T		intron	N/A	ENSP00000276393.4

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107041 AN: 151798 Hom.: 38124 Cov.: 33

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.705 AC: 107123 AN: 151918 Hom.: 38154 Cov.: 33 AF XY: 0.702 AC XY: 52147 AN XY: 74254

African (AFR) AF: 0.782 AC: 32420 AN: 41480

American (AMR) AF: 0.620 AC: 9469 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2163 AN: 3466

East Asian (EAS) AF: 0.527 AC: 2720 AN: 5160

South Asian (SAS) AF: 0.595 AC: 2862 AN: 4810

European-Finnish (FIN) AF: 0.703 AC: 7403 AN: 10532

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.706 AC: 47900 AN: 67880

Other (OTH) AF: 0.680 AC: 1438 AN: 2114

Alfa AF: 0.696 Hom.: 14409

Bravo AF: 0.697

Asia WGS AF: 0.592 AC: 2059 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.48
PhyloP100		0.48
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: rs520180; hg19: chr8-26709922;