rs4732957

Positions:

• chr8-26861363-A-C
• chr8-26861363-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000680.4(ADRA1A):​c.883+2724T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 144,822 control chromosomes in the GnomAD database, including 32,984 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 0.66 (32984 hom., cov: 21)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRA1A	NM_000680.4	c.883+2724T>G		intron_variant		ENST00000380573.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRA1A	ENST00000380573.4	c.883+2724T>G		intron_variant		2	NM_000680.4	P1

Frequencies

GnomAD3 genomes AF: 0.657 AC: 95050 AN: 144708 Hom.: 32981 Cov.: 21

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.946

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.657 AC: 95083 AN: 144822 Hom.: 32984 Cov.: 21 AF XY: 0.661 AC XY: 46352 AN XY: 70084

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.787

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.646

Alfa AF: 0.686 Hom.: 3894

Bravo AF: 0.628

Asia WGS AF: 0.742 AC: 2581 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs4732957; hg19: chr8-26718880;