dbSNP rs1383914: ADRA1A:c.-563A>G (chr8-26865532-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000680.4(ADRA1A):c.-563A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 991,098 control chromosomes in the GnomAD database, including 120,081 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 0.48 ( 17339 hom., cov: 31)

Exomes 𝑓: 0.49 ( 102742 hom. )

Consequence

ADRA1A
NM_000680.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

19 publications found

Variant links:

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]

ADRA1A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1A	NM_000680.4 link	c.-563A>G		5_prime_UTR_variant	Exon 2 of 3	ENST00000380573.4	NP_000671.2	P35348-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA1A	ENST00000380573.4 link	c.-563A>G		5_prime_UTR_variant	Exon 2 of 3	2	NM_000680.4	ENSP00000369947.3		P35348-1

Frequencies

GnomAD3 genomes

AF:

0.477

AC:

72311

AN:

151552

Hom.:

17329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.448

Gnomad AMI

AF:

0.558

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.498

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.603

Gnomad FIN

AF:

0.482

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.483

Gnomad OTH

AF:

0.460

GnomAD4 exome

AF:

0.494

AC:

415074

AN:

839428

Hom.:

102742

Cov.:

AF XY:

0.494

AC XY:

191740

AN XY:

388010

show subpopulations

African (AFR)

AF:

0.453

AC:

7172

AN:

15818

American (AMR)

AF:

0.457

AC:

1207

AN:

2644

Ashkenazi Jewish (ASJ)

AF:

0.499

AC:

2587

AN:

5186

East Asian (EAS)

AF:

0.541

AC:

2028

AN:

3750

South Asian (SAS)

AF:

0.590

AC:

10089

AN:

17104

European-Finnish (FIN)

AF:

0.489

AC:

174

AN:

356

Middle Eastern (MID)

AF:

0.523

AC:

851

AN:

1628

European-Non Finnish (NFE)

AF:

0.493

AC:

377386

AN:

765394

Other (OTH)

AF:

0.493

AC:

13580

AN:

27548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

12603

25205

37808

50410

63013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15152

30304

45456

60608

75760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.477

AC:

72350

AN:

151670

Hom.:

17339

Cov.:

AF XY:

0.484

AC XY:

35832

AN XY:

74072

show subpopulations

African (AFR)

AF:

0.448

AC:

18522

AN:

41354

American (AMR)

AF:

0.457

AC:

6978

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.498

AC:

1730

AN:

3472

East Asian (EAS)

AF:

0.542

AC:

2763

AN:

5102

South Asian (SAS)

AF:

0.603

AC:

2895

AN:

4800

European-Finnish (FIN)

AF:

0.482

AC:

5059

AN:

10494

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.483

AC:

32777

AN:

67876

Other (OTH)

AF:

0.459

AC:

967

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1967

3934

5900

7867

9834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.483

Hom.:

56991

Bravo

AF:

0.472

Asia WGS

AF:

0.554

AC:

1927

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

1.1

PromoterAI

-0.026

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over