Variant rs2229126 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000680.4(ADRA1A):c.1395A>T(p.Glu465Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,547,296 control chromosomes in the GnomAD database, including 805 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.029 ( 83 hom., cov: 32)

Exomes 𝑓: 0.029 ( 722 hom. )

Consequence

ADRA1A
NM_000680.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.110

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:

ADRA1A (HGNC:):

ADRA1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014440715).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA1A	NM_000680.4 linkuse as main transcript	c.1395A>T	p.Glu465Asp	missense_variant	3/3	ENST00000380573.4	NP_000671.2	P35348-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA1A	ENST00000380573.4 linkuse as main transcript	c.1395A>T	p.Glu465Asp	missense_variant	3/3	2	NM_000680.4	ENSP00000369947.3		P35348-1

Frequencies

GnomAD3 genomes

AF:

0.0294

AC:

4469

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0242

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0611

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.0449

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.0291

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0263

Gnomad OTH

AF:

0.0259

GnomAD3 exomes

AF:

0.0362

AC:

7284

AN:

200972

Hom.:

201

AF XY:

0.0335

AC XY:

3543

AN XY:

105836

show subpopulations

Gnomad AFR exome

AF:

0.0250

Gnomad AMR exome

AF:

0.0857

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.0520

Gnomad SAS exome

AF:

0.0163

Gnomad FIN exome

AF:

0.0279

Gnomad NFE exome

AF:

0.0279

Gnomad OTH exome

AF:

0.0321

GnomAD4 exome

AF:

0.0287

AC:

40097

AN:

1395052

Hom.:

722

Cov.:

AF XY:

0.0280

AC XY:

19199

AN XY:

685884

show subpopulations

Gnomad4 AFR exome

AF:

0.0250

Gnomad4 AMR exome

AF:

0.0782

Gnomad4 ASJ exome

AF:

0.0136

Gnomad4 EAS exome

AF:

0.0372

Gnomad4 SAS exome

AF:

0.0159

Gnomad4 FIN exome

AF:

0.0264

Gnomad4 NFE exome

AF:

0.0281

Gnomad4 OTH exome

AF:

0.0308

GnomAD4 genome

AF:

0.0293

AC:

4468

AN:

152244

Hom.:

Cov.:

AF XY:

0.0304

AC XY:

2261

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0242

Gnomad4 AMR

AF:

0.0612

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.0445

Gnomad4 SAS

AF:

0.0135

Gnomad4 FIN

AF:

0.0291

Gnomad4 NFE

AF:

0.0263

Gnomad4 OTH

AF:

0.0261

Alfa

AF:

0.0228

Hom.:

Bravo

AF:

0.0328

TwinsUK

AF:

0.0262

AC:

ALSPAC

AF:

0.0267

AC:

103

ESP6500AA

AF:

0.0236

AC:

104

ESP6500EA

AF:

0.0244

AC:

210

ExAC

AF:

0.0314

AC:

3792

Asia WGS

AF:

0.0350

AC:

120

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.033

T;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.51

.;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.22

N;N

REVEL

Benign

0.23

Sift

Benign

0.49

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.0

B;B

Vest4

0.20

MutPred

0.026

Loss of disorder (P = 0.3186);Loss of disorder (P = 0.3186);

ClinPred

0.013

GERP RS

2.1

Varity_R

0.044

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over