rs486354

Variant names:

• chr8-26852773-A-G
• rs486354
• NM_000680.4:c.883+11314T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-26852773-A-G
• chr8-26852773-A-T

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+11314T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,104 control chromosomes in the GnomAD database, including 4,728 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 0.24 (4728 hom., cov: 33)
• Consequence: ADRA1A NM_000680.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 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+11314T>C		intron	N/A	NP_000671.2	P35348-1
	ADRA1A	NM_033303.4		c.883+11314T>C		intron	N/A	NP_150646.3	B0ZBD3
	ADRA1A	NM_033304.3		c.883+11314T>C		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+11314T>C		intron	N/A	ENSP00000369947.3	P35348-1
	ADRA1A	ENST00000380586.5	TSL:1	c.883+11314T>C		intron	N/A	ENSP00000369960.1	P35348-2
	ADRA1A	ENST00000276393.8	TSL:1	c.883+11314T>C		intron	N/A	ENSP00000276393.4	P35348-1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36641 AN: 151986 Hom.: 4729 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.241 AC: 36650 AN: 152104 Hom.: 4728 Cov.: 33 AF XY: 0.235 AC XY: 17491 AN XY: 74350

African (AFR) AF: 0.179 AC: 7436 AN: 41550

American (AMR) AF: 0.204 AC: 3123 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1051 AN: 3464

East Asian (EAS) AF: 0.128 AC: 665 AN: 5188

South Asian (SAS) AF: 0.0999 AC: 482 AN: 4826

European-Finnish (FIN) AF: 0.271 AC: 2868 AN: 10572

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20097 AN: 67908

Other (OTH) AF: 0.241 AC: 508 AN: 2104

Alfa AF: 0.264 Hom.: 2179

Bravo AF: 0.236

Asia WGS AF: 0.108 AC: 379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.44
PhyloP100		0.027
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: rs486354; hg19: chr8-26710290;