Variant 8-26864510-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000680.4(ADRA1A):c.460T>G(p.Ser154Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00888 in 1,613,934 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 12 hom., cov: 32)

Exomes 𝑓: 0.0091 ( 99 hom. )

Consequence

ADRA1A
NM_000680.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.35

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011062622).

BP6

Variant 8-26864510-A-C is Benign according to our data. Variant chr8-26864510-A-C is described in ClinVar as [Benign]. Clinvar id is 778029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA1A	NM_000680.4 link	c.460T>G	p.Ser154Ala	missense_variant	2/3	ENST00000380573.4	NP_000671.2	P35348-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA1A	ENST00000380573.4 link	c.460T>G	p.Ser154Ala	missense_variant	2/3	2	NM_000680.4	ENSP00000369947.3		P35348-1

Frequencies

GnomAD3 genomes

AF:

0.00709

AC:

1078

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.00537

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0169

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00768

GnomAD3 exomes

AF:

0.00695

AC:

1745

AN:

251160

Hom.:

AF XY:

0.00676

AC XY:

918

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.00419

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.0157

Gnomad NFE exome

AF:

0.0104

Gnomad OTH exome

AF:

0.00702

GnomAD4 exome

AF:

0.00907

AC:

13260

AN:

1461744

Hom.:

Cov.:

AF XY:

0.00894

AC XY:

6498

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.00420

Gnomad4 ASJ exome

AF:

0.000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.0162

Gnomad4 NFE exome

AF:

0.0105

Gnomad4 OTH exome

AF:

0.00730

GnomAD4 genome

AF:

0.00708

AC:

1078

AN:

152190

Hom.:

Cov.:

AF XY:

0.00695

AC XY:

517

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0169

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.00760

Alfa

AF:

0.00840

Hom.:

Bravo

AF:

0.00616

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0117

AC:

101

ExAC

AF:

0.00645

AC:

783

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0105

EpiControl

AF:

0.00871

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

.;.;.;.;T;T;.

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.81

T;T;T;T;.;T;T

MetaRNN

Benign

0.011

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L;.;L;L;L;L

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.3

N;N;N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.094

T;T;T;T;T;T;T

Sift4G

Benign

0.21

T;T;T;T;T;T;T

Polyphen

0.32, 0.81, 0.93

.;B;.;P;P;P;.

Vest4

0.28

MVP

0.57

MPC

0.65

ClinPred

0.088

GERP RS

3.7

Varity_R

0.33

gMVP

0.92

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over