8-26840954-T-C

Variant names:

• chr8-26840954-T-C
• rs472865
• NM_000680.4:c.883+23133A>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.883+23133A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.883 in 152,228 control chromosomes in the GnomAD database, including 59,571 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 (59571 hom., cov: 32)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 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.883+23133A>G		intron	N/A	NP_000671.2	P35348-1
	ADRA1A	NM_033303.4		c.883+23133A>G		intron	N/A	NP_150646.3	B0ZBD3
	ADRA1A	NM_033304.3		c.883+23133A>G		intron	N/A	NP_150647.2	P35348-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1A	ENST00000380573.4	TSL:2 MANE Select	c.883+23133A>G		intron	N/A	ENSP00000369947.3	P35348-1
	ADRA1A	ENST00000380586.5	TSL:1	c.883+23133A>G		intron	N/A	ENSP00000369960.1	P35348-2
	ADRA1A	ENST00000276393.8	TSL:1	c.883+23133A>G		intron	N/A	ENSP00000276393.4	P35348-1

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134253 AN: 152110 Hom.: 59517 Cov.: 32

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.887

Gnomad OTH AF: 0.864

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

GnomAD4 genome AF: 0.883 AC: 134362 AN: 152228 Hom.: 59571 Cov.: 32 AF XY: 0.880 AC XY: 65511 AN XY: 74414

African (AFR) AF: 0.938 AC: 38954 AN: 41542

American (AMR) AF: 0.794 AC: 12142 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 2905 AN: 3472

East Asian (EAS) AF: 0.710 AC: 3672 AN: 5170

South Asian (SAS) AF: 0.780 AC: 3759 AN: 4822

European-Finnish (FIN) AF: 0.918 AC: 9731 AN: 10602

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.887 AC: 60342 AN: 68012

Other (OTH) AF: 0.863 AC: 1822 AN: 2112

Alfa AF: 0.871 Hom.: 58030

Bravo AF: 0.874

Asia WGS AF: 0.763 AC: 2656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.021
DANN	Benign	0.57
PhyloP100		-2.7
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: rs472865; hg19: chr8-26698471;