dbSNP rs2236554: ADRA1D:c.*129A>T (chr20-4221394-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000678.4(ADRA1D):c.*129A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,060,912 control chromosomes in the GnomAD database, including 80,942 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 0.32 ( 8647 hom., cov: 33)

Exomes 𝑓: 0.40 ( 72295 hom. )

Consequence

ADRA1D
NM_000678.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.562

Publications

18 publications found

Variant links:

Genes affected

ADRA1D (HGNC:280): (adrenoceptor alpha 1D) 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-1D-adrenergic receptor. Similar to alpha-1B-adrenergic receptor gene, this gene comprises 2 exons and a single intron that interrupts the coding region. [provided by RefSeq, Jul 2008]

ADRA1D links:

Genome browser will be placed here

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=-0.76).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1D	NM_000678.4 link	c.*129A>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000379453.6	NP_000669.1	P25100B0ZBE0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA1D	ENST00000379453.6 link	c.*129A>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_000678.4	ENSP00000368766.4		P25100

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48694

AN:

151984

Hom.:

8643

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.345

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.334

Gnomad SAS

AF:

0.517

Gnomad FIN

AF:

0.317

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.346

GnomAD4 exome

AF:

0.395

AC:

359164

AN:

908812

Hom.:

72295

Cov.:

AF XY:

0.400

AC XY:

181763

AN XY:

454882

show subpopulations

African (AFR)

AF:

0.161

AC:

3202

AN:

19944

American (AMR)

AF:

0.288

AC:

6583

AN:

22824

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

6281

AN:

16156

East Asian (EAS)

AF:

0.299

AC:

9978

AN:

33322

South Asian (SAS)

AF:

0.503

AC:

27115

AN:

53938

European-Finnish (FIN)

AF:

0.301

AC:

14008

AN:

46566

Middle Eastern (MID)

AF:

0.343

AC:

968

AN:

2822

European-Non Finnish (NFE)

AF:

0.410

AC:

275616

AN:

672494

Other (OTH)

AF:

0.378

AC:

15413

AN:

40746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

10696

21392

32089

42785

53481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7478

14956

22434

29912

37390

<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:

0.320

AC:

48717

AN:

152100

Hom.:

8647

Cov.:

AF XY:

0.321

AC XY:

23857

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.164

AC:

6807

AN:

41518

American (AMR)

AF:

0.331

AC:

5067

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

1351

AN:

3472

East Asian (EAS)

AF:

0.334

AC:

1725

AN:

5170

South Asian (SAS)

AF:

0.517

AC:

2489

AN:

4818

European-Finnish (FIN)

AF:

0.317

AC:

3352

AN:

10578

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.394

AC:

26778

AN:

67934

Other (OTH)

AF:

0.345

AC:

731

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1675

3349

5024

6698

8373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

502

1004

1506

2008

2510

<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:

0.338

Hom.:

1266

Bravo

AF:

0.312

Asia WGS

AF:

0.405

AC:

1410

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.2

(source)

DANN

Benign

0.79

PhyloP100

-0.56

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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