dbSNP rs6884105: ADRA1B:c.949+3582G>A (chr5-159921436-G-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_000679.4(ADRA1B):c.949+3582G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,048 control chromosomes in the GnomAD database, including 13,502 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 0.41 ( 13502 hom., cov: 33)

Consequence

ADRA1B
NM_000679.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.924

Publications

5 publications found

Variant links:

Genes affected

ADRA1B (HGNC:278): (adrenoceptor alpha 1B) 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-1B-adrenergic receptor, which induces neoplastic transformation when transfected into NIH 3T3 fibroblasts and other cell lines. Thus, this normal cellular gene is identified as a protooncogene. This gene comprises 2 exons and a single large intron of at least 20 kb that interrupts the coding region. [provided by RefSeq, Jul 2008]

ADRA1B links:

LINC01847 (HGNC:52662): (long intergenic non-protein coding RNA 1847)

LINC01847 links:

ENSG00000306315 (HGNC:):

ENSG00000306315 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA1B	NM_000679.4 link	c.949+3582G>A		intron_variant	Intron 1 of 1	ENST00000306675.5	NP_000670.1	P35368

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADRA1B	ENST00000306675.5 link	c.949+3582G>A	intron_variant	Intron 1 of 1	1	NM_000679.4	ENSP00000306662.3	P35368
LINC01847	ENST00000641163.1 link	n.181+7599C>T	intron_variant	Intron 2 of 7
LINC01847	ENST00000816795.1 link	n.142+7599C>T	intron_variant	Intron 2 of 3
ENSG00000306315	ENST00000816922.1 link	n.52+505G>A	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.409

AC:

62213

AN:

151930

Hom.:

13471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.505

Gnomad AMI

AF:

0.461

Gnomad AMR

AF:

0.391

Gnomad ASJ

AF:

0.330

Gnomad EAS

AF:

0.744

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.325

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.396

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.410

AC:

62286

AN:

152048

Hom.:

13502

Cov.:

AF XY:

0.411

AC XY:

30527

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.506

AC:

20952

AN:

41444

American (AMR)

AF:

0.391

AC:

5966

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

1146

AN:

3468

East Asian (EAS)

AF:

0.744

AC:

3850

AN:

5172

South Asian (SAS)

AF:

0.396

AC:

1908

AN:

4818

European-Finnish (FIN)

AF:

0.325

AC:

3433

AN:

10570

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.348

AC:

23643

AN:

67994

Other (OTH)

AF:

0.400

AC:

845

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1827

3655

5482

7310

9137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

588

1176

1764

2352

2940

<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:

0.371

Hom.:

30708

Bravo

AF:

0.418

Asia WGS

AF:

0.545

AC:

1896

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.092

(source)

DANN

Benign

0.19

PhyloP100

-0.92

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over