8-26866167-C-T

Variant names:

• chr8-26866167-C-T
• rs574584
• NM_000680.4:c.-686-512G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000680.4(ADRA1A):​c.-686-512G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 152,120 control chromosomes in the GnomAD database, including 59,168 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 (59168 hom., cov: 31)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.822
• Publications: 10 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.948 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1A	NM_000680.4	MANE Select	c.-686-512G>A		intron	N/A	NP_000671.2	P35348-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1A	ENST00000380573.4	TSL:2 MANE Select	c.-686-512G>A		intron	N/A	ENSP00000369947.3	P35348-1
	ENSG00000303788	ENST00000797227.1		n.-1C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133053 AN: 152002 Hom.: 59147 Cov.: 31

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.982

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.883

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

GnomAD4 genome AF: 0.875 AC: 133126 AN: 152120 Hom.: 59168 Cov.: 31 AF XY: 0.877 AC XY: 65210 AN XY: 74366

African (AFR) AF: 0.705 AC: 29237 AN: 41464

American (AMR) AF: 0.874 AC: 13370 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.986 AC: 3425 AN: 3472

East Asian (EAS) AF: 0.909 AC: 4671 AN: 5136

South Asian (SAS) AF: 0.933 AC: 4502 AN: 4824

European-Finnish (FIN) AF: 0.942 AC: 9998 AN: 10608

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.954 AC: 64894 AN: 68006

Other (OTH) AF: 0.879 AC: 1858 AN: 2114

Alfa AF: 0.909 Hom.: 7443

Bravo AF: 0.862

Asia WGS AF: 0.885 AC: 3080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	8.3
DANN	Benign	0.96
PhyloP100		0.82
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: rs574584; hg19: chr8-26723684; COSMIC: COSV52375152; COSMIC: COSV52375152;