Genetic Variant ADRA1B:p.Pro325Thr (chr5-159971902-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000679.4(ADRA1B):c.973C>A(p.Pro325Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000004 in 999,550 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000040 ( 0 hom. )

Consequence

ADRA1B
NM_000679.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000679.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1B	NM_000679.4	MANE Select	c.973C>A	p.Pro325Thr	missense	Exon 2 of 2	NP_000670.1	P35368

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRA1B	ENST00000306675.5	TSL:1 MANE Select	c.973C>A	p.Pro325Thr	missense	Exon 2 of 2	ENSP00000306662.3	P35368
	ADRA1B	ENST00000865014.1		c.973C>A	p.Pro325Thr	missense	Exon 5 of 5	ENSP00000535073.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000400

AC:

AN:

999550

Hom.:

Cov.:

AF XY:

0.00000207

AC XY:

AN XY:

483414

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20096

American (AMR)

AF:

0.00

AC:

AN:

14664

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11426

East Asian (EAS)

AF:

0.00

AC:

AN:

13374

South Asian (SAS)

AF:

0.00

AC:

AN:

35122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3776

European-Non Finnish (NFE)

AF:

0.00000476

AC:

AN:

840878

Other (OTH)

AF:

0.00

AC:

AN:

35244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.78

Eigen

Benign

0.17

Eigen_PC

Benign

0.15

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.86

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.63

MetaSVM

Uncertain

-0.20

MutationAssessor

Benign

1.3

PhyloP100

3.8

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.31

Sift

Benign

0.082

Sift4G

Benign

0.15

Polyphen

0.87

Vest4

0.53

MutPred

0.51

Loss of catalytic residue at P325 (P = 0.07)

MVP

0.83

MPC

1.2

ClinPred

0.99

GERP RS

1.5

Varity_R

0.56

gMVP

0.66

Mutation Taster

=62/38

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over