NM_000680.4:c.-687+519A>G

Variant names:

• chr8-26866417-T-C
• rs486179
• NM_000680.4:c.-687+519A>G

Variant summary

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

The NM_000680.4(ADRA1A):​c.-687+519A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,182 control chromosomes in the GnomAD database, including 59,572 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 0.88 (59572 hom., cov: 31)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 8 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]

ENSG00000303788 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 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.-687+519A>G		intron	N/A	NP_000671.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1A	ENST00000380573.4	TSL:2 MANE Select	c.-687+519A>G		intron	N/A	ENSP00000369947.3
	ENSG00000303788	ENST00000797227.1		n.124+126T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133546 AN: 152064 Hom.: 59542 Cov.: 31

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.987

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.887

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

GnomAD4 genome AF: 0.878 AC: 133629 AN: 152182 Hom.: 59572 Cov.: 31 AF XY: 0.879 AC XY: 65414 AN XY: 74386

African (AFR) AF: 0.713 AC: 29616 AN: 41512

American (AMR) AF: 0.878 AC: 13440 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.987 AC: 3426 AN: 3472

East Asian (EAS) AF: 0.909 AC: 4656 AN: 5122

South Asian (SAS) AF: 0.933 AC: 4500 AN: 4824

European-Finnish (FIN) AF: 0.942 AC: 10001 AN: 10614

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.955 AC: 64954 AN: 68016

Other (OTH) AF: 0.883 AC: 1864 AN: 2112

Alfa AF: 0.934 Hom.: 30324

Bravo AF: 0.866

Asia WGS AF: 0.890 AC: 3097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.37
PhyloP100		0.071
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: rs486179; hg19: chr8-26723934;