rs4732957

Variant names:

• chr8-26861363-A-C
• rs4732957
• NM_000680.4:c.883+2724T>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_033303.4(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_033303.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518
• Publications: 3 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=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033303.4. 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.883+2724T>G		intron	N/A	NP_000671.2
	ADRA1A	NM_033303.4		c.883+2724T>G		intron	N/A	NP_150646.3
	ADRA1A	NM_033304.3		c.883+2724T>G		intron	N/A	NP_150647.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1A	ENST00000380573.4	TSL:2 MANE Select	c.883+2724T>G		intron	N/A	ENSP00000369947.3
	ADRA1A	ENST00000380586.5	TSL:1	c.883+2724T>G		intron	N/A	ENSP00000369960.1
	ADRA1A	ENST00000276393.8	TSL:1	c.883+2724T>G		intron	N/A	ENSP00000276393.4

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

African (AFR) AF: 0.414 AC: 15851 AN: 38324

American (AMR) AF: 0.606 AC: 8765 AN: 14472

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2739 AN: 3438

East Asian (EAS) AF: 0.762 AC: 3737 AN: 4902

South Asian (SAS) AF: 0.787 AC: 3502 AN: 4452

European-Finnish (FIN) AF: 0.799 AC: 7245 AN: 9070

Middle Eastern (MID) AF: 0.729 AC: 210 AN: 288

European-Non Finnish (NFE) AF: 0.760 AC: 50885 AN: 66970

Other (OTH) AF: 0.646 AC: 1294 AN: 2002

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.17
PhyloP100		-0.52
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: rs4732957; hg19: chr8-26718880;