8-26840954-T-C

Position:

• chr8-26840954-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA1A	NM_000680.4	c.883+23133A>G		intron_variant		ENST00000380573.4	NP_000671.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA1A	ENST00000380573.4	c.883+23133A>G		intron_variant		2	NM_000680.4	ENSP00000369947	P1

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

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.837

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.918

Gnomad4 NFE AF: 0.887

Gnomad4 OTH AF: 0.863

Alfa AF: 0.872 Hom.: 41150

Bravo AF: 0.874

Asia WGS AF: 0.763 AC: 2656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.021
DANN	Benign	0.57

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: rs472865; hg19: chr8-26698471;