dbSNP rs7434444: ADRA2C:c.*347G>C (chr4-3768342-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_000683.4(ADRA2C):c.*347G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 714,670 control chromosomes in the GnomAD database, including 37,649 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 0.37 ( 12820 hom., cov: 32)

Exomes 𝑓: 0.28 ( 24829 hom. )

Consequence

ADRA2C
NM_000683.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Publications

10 publications found

Variant links:

Genes affected

ADRA2C (HGNC:283): (adrenoceptor alpha 2C) Alpha-2-adrenergic receptors are members of the G protein-coupled receptor superfamily. They include 3 highly homologous subtypes: alpha2A, alpha2B, and alpha2C. These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. The mouse studies revealed that both the alpha2A and alpha2C subtypes were required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons. The alpha2A subtype inhibited transmitter release at high stimulation frequencies, whereas the alpha2C subtype modulated neurotransmission at lower levels of nerve activity. This gene encodes the alpha2C subtype, which contains no introns in either its coding or untranslated sequences. [provided by RefSeq, Jul 2008]

ADRA2C 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 (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA2C	NM_000683.4 link	c.*347G>C		3_prime_UTR_variant	Exon 1 of 1	ENST00000330055.7	NP_000674.2	P18825Q4W594

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA2C	ENST00000330055.7 link	c.*347G>C		3_prime_UTR_variant	Exon 1 of 1	6	NM_000683.4	ENSP00000386069.2		P18825
ADRA2C	ENST00000509482.1 link	c.*67G>C		3_prime_UTR_variant	Exon 2 of 2	3		ENSP00000426268.1		D6RGL0

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56179

AN:

151938

Hom.:

12787

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.293

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.285

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.313

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.257

Gnomad OTH

AF:

0.313

GnomAD4 exome

AF:

0.283

AC:

159476

AN:

562614

Hom.:

24829

Cov.:

AF XY:

0.290

AC XY:

88088

AN XY:

303552

show subpopulations

African (AFR)

AF:

0.637

AC:

10058

AN:

15784

American (AMR)

AF:

0.178

AC:

6128

AN:

34488

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

3929

AN:

19824

East Asian (EAS)

AF:

0.227

AC:

7278

AN:

32076

South Asian (SAS)

AF:

0.412

AC:

25697

AN:

62304

European-Finnish (FIN)

AF:

0.315

AC:

14973

AN:

47582

Middle Eastern (MID)

AF:

0.278

AC:

1130

AN:

4062

European-Non Finnish (NFE)

AF:

0.257

AC:

81220

AN:

315922

Other (OTH)

AF:

0.296

AC:

9063

AN:

30572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

6108

12216

18325

24433

30541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.370

AC:

56270

AN:

152056

Hom.:

12820

Cov.:

AF XY:

0.373

AC XY:

27699

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.645

AC:

26752

AN:

41464

American (AMR)

AF:

0.235

AC:

3593

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

666

AN:

3472

East Asian (EAS)

AF:

0.286

AC:

1474

AN:

5160

South Asian (SAS)

AF:

0.409

AC:

1969

AN:

4816

European-Finnish (FIN)

AF:

0.313

AC:

3314

AN:

10580

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.257

AC:

17495

AN:

67956

Other (OTH)

AF:

0.313

AC:

662

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1570

3140

4710

6280

7850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.327

Hom.:

1286

Bravo

AF:

0.371

Asia WGS

AF:

0.363

AC:

1263

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.7

(source)

DANN

Benign

0.65

PhyloP100

-1.0

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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rs7434444

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