Genetic Variant ADRA1A:c.*417C>G (chr8-26769732-G-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.*417C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0758 in 990,204 control chromosomes in the GnomAD database, including 4,363 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 0.12 ( 1786 hom., cov: 32)

Exomes 𝑓: 0.067 ( 2577 hom. )

Consequence

ADRA1A
NM_000680.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.270

Publications

10 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADRA1A	NM_000680.4	MANE Select	c.*417C>G	3_prime_UTR	Exon 3 of 3	NP_000671.2
ADRA1A	NM_033303.4		c.1269+549C>G	intron	N/A	NP_150646.3
ADRA1A	NM_033304.3		c.1269+549C>G	intron	N/A	NP_150647.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADRA1A	ENST00000380573.4	TSL:2 MANE Select	c.*417C>G	3_prime_UTR	Exon 3 of 3	ENSP00000369947.3
ADRA1A	ENST00000276393.8	TSL:1	c.*417C>G	3_prime_UTR	Exon 2 of 2	ENSP00000276393.4
ADRA1A	ENST00000380586.5	TSL:1	c.1269+549C>G	intron	N/A	ENSP00000369960.1

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18870

AN:

152002

Hom.:

1787

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.0672

Gnomad EAS

AF:

0.448

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.0375

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0635

Gnomad OTH

AF:

0.112

GnomAD4 exome

AF:

0.0670

AC:

56160

AN:

838084

Hom.:

2577

Cov.:

AF XY:

0.0666

AC XY:

25777

AN XY:

387162

show subpopulations

African (AFR)

AF:

0.203

AC:

3232

AN:

15924

American (AMR)

AF:

0.146

AC:

204

AN:

1394

Ashkenazi Jewish (ASJ)

AF:

0.0573

AC:

306

AN:

5340

East Asian (EAS)

AF:

0.449

AC:

1683

AN:

3746

South Asian (SAS)

AF:

0.176

AC:

2909

AN:

16546

European-Finnish (FIN)

AF:

0.0407

AC:

AN:

418

Middle Eastern (MID)

AF:

0.113

AC:

184

AN:

1630

European-Non Finnish (NFE)

AF:

0.0587

AC:

44896

AN:

765490

Other (OTH)

AF:

0.0989

AC:

2729

AN:

27596

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

2744

5488

8233

10977

13721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2450

4900

7350

9800

12250

<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:

0.124

AC:

18886

AN:

152120

Hom.:

1786

Cov.:

AF XY:

0.126

AC XY:

9390

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.193

AC:

8004

AN:

41470

American (AMR)

AF:

0.156

AC:

2382

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0672

AC:

233

AN:

3466

East Asian (EAS)

AF:

0.448

AC:

2316

AN:

5168

South Asian (SAS)

AF:

0.192

AC:

922

AN:

4798

European-Finnish (FIN)

AF:

0.0375

AC:

398

AN:

10610

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0635

AC:

4320

AN:

68004

Other (OTH)

AF:

0.114

AC:

240

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

763

1526

2290

3053

3816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

210

420

630

840

1050

<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:

0.0404

Hom.:

Bravo

AF:

0.136

Asia WGS

AF:

0.305

AC:

1058

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.60

(source)

DANN

Benign

0.56

PhyloP100

-0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over