Genetic Variant ADRB1:p.Arg318Cys (chr10-114045084-C-T) – 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_000684.3(ADRB1):c.952C>T(p.Arg318Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,331,998 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

ADRB1
NM_000684.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.04

Publications

0 publications found

Variant links:

Genes affected

ADRB1 (HGNC:285): (adrenoceptor beta 1) The adrenergic receptors (subtypes alpha 1, alpha 2, beta 1, and beta 2) are a prototypic family of guanine nucleotide binding regulatory protein-coupled receptors that mediate the physiological effects of the hormone epinephrine and the neurotransmitter norepinephrine. Beta-1 adrenoceptors are predominately located in the heart. Specific polymorphisms in this gene have been shown to affect the resting heart rate and can be involved in heart failure. [provided by RefSeq, Sep 2019]

ADRB1 links:

Genome browser will be placed here

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;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB1	NM_000684.3 link	c.952C>T	p.Arg318Cys	missense_variant	Exon 1 of 1	ENST00000369295.4	NP_000675.1	P08588

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRB1	ENST00000369295.4 link	c.952C>T	p.Arg318Cys	missense_variant	Exon 1 of 1	6	NM_000684.3	ENSP00000358301.2		P08588

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000753

AC:

AN:

132842

AF XY:

0.0000134

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000150

AC:

AN:

1331998

Hom.:

Cov.:

AF XY:

0.00000303

AC XY:

AN XY:

659846

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27776

American (AMR)

AF:

0.00

AC:

AN:

31826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23180

East Asian (EAS)

AF:

0.00

AC:

AN:

29806

South Asian (SAS)

AF:

0.0000135

AC:

AN:

74188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40942

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4848

European-Non Finnish (NFE)

AF:

9.57e-7

AC:

AN:

1045266

Other (OTH)

AF:

0.00

AC:

AN:

54166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000168

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.87

M_CAP

Pathogenic

0.96

MetaRNN

Uncertain

0.68

MetaSVM

Uncertain

0.46

PhyloP100

2.0

PrimateAI

Pathogenic

0.93

PROVEAN

Pathogenic

-5.4

REVEL

Uncertain

0.62

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.22

MutPred

0.66

Loss of MoRF binding (P = 0.017);

MVP

0.84

ClinPred

0.99

GERP RS

2.8

gMVP

0.81

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over