rs1801253

Variant names:

• chr10-114045297-G-C
• rs1801253
• NM_000684.3:c.1165G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-114045297-G-C
• chr10-114045297-G-A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000684.3(ADRB1):​c.1165G>C​(p.Gly389Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,577,268 control chromosomes in the GnomAD database, including 423,077 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,association (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G389V) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.70 (36948 hom., cov: 34)
  • Exomes 𝑓: 0.73 (386129 hom.)
• Consequence: ADRB1 NM_000684.3 missense
• Clinical Significance: Benign; association no assertion criteria provided B:2 O:1
• Conservation: PhyloP100: 1.04
• Publications: 603 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.993127E-7).
• BP6: Variant 10-114045297-G-C is Benign according to our data. Variant chr10-114045297-G-C is described in ClinVar as Benign|association. ClinVar VariationId is 17746.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000684.3. 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
	ADRB1	NM_000684.3	MANE Select	c.1165G>C	p.Gly389Arg	missense	Exon 1 of 1	NP_000675.1	P08588

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRB1	ENST00000369295.4	TSL:6 MANE Select	c.1165G>C	p.Gly389Arg	missense	Exon 1 of 1	ENSP00000358301.2	P08588

Frequencies

GnomAD3 genomes AF: 0.696 AC: 104769 AN: 150514 Hom.: 36905 Cov.: 34

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.681

GnomAD2 exomes AF: 0.737 AC: 162149 AN: 219864 AF XY: 0.735

Gnomad AFR exome AF: 0.578

Gnomad AMR exome AF: 0.859

Gnomad ASJ exome AF: 0.625

Gnomad EAS exome AF: 0.745

Gnomad FIN exome AF: 0.739

Gnomad NFE exome AF: 0.725

Gnomad OTH exome AF: 0.717

GnomAD4 exome AF: 0.734 AC: 1047689 AN: 1426646 Hom.: 386129 Cov.: 58 AF XY: 0.735 AC XY: 521652 AN XY: 709768

African (AFR) AF: 0.579 AC: 18120 AN: 31314

American (AMR) AF: 0.846 AC: 35078 AN: 41450

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 15648 AN: 25222

East Asian (EAS) AF: 0.781 AC: 28390 AN: 36338

South Asian (SAS) AF: 0.755 AC: 62671 AN: 82964

European-Finnish (FIN) AF: 0.746 AC: 38391 AN: 51444

Middle Eastern (MID) AF: 0.614 AC: 3476 AN: 5664

European-Non Finnish (NFE) AF: 0.735 AC: 803713 AN: 1093620

Other (OTH) AF: 0.720 AC: 42202 AN: 58630

GnomAD4 genome AF: 0.696 AC: 104861 AN: 150622 Hom.: 36948 Cov.: 34 AF XY: 0.699 AC XY: 51435 AN XY: 73560

African (AFR) AF: 0.593 AC: 24506 AN: 41352

American (AMR) AF: 0.777 AC: 11790 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2143 AN: 3452

East Asian (EAS) AF: 0.763 AC: 3932 AN: 5154

South Asian (SAS) AF: 0.738 AC: 3567 AN: 4832

European-Finnish (FIN) AF: 0.743 AC: 7351 AN: 9898

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.732 AC: 49413 AN: 67466

Other (OTH) AF: 0.681 AC: 1421 AN: 2088

Alfa AF: 0.709 Hom.: 12411

Bravo AF: 0.693

TwinsUK AF: 0.724 AC: 2685

ALSPAC AF: 0.752 AC: 2897

ESP6500AA AF: 0.627 AC: 2565

ESP6500EA AF: 0.736 AC: 5915

ExAC AF: 0.727 AC: 85629

Asia WGS AF: 0.732 AC: 2456 AN: 3356

ClinVar

ClinVar submissions

Significance: Benign; association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ADRB1-related disorder (1)
-	-	1	not provided (1)
-	-	-	Pulmonary disease, chronic obstructive, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.66
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.34	N
MetaRNN	Benign	8.0e-7	T
MetaSVM	Benign	-0.96	T
PhyloP100		1.0
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	3.2	N
REVEL	Benign	0.070
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.055
MutPred		0.32		Gain of MoRF binding (P = 0.02)
ClinPred		0.0049	T
GERP RS		1.7
gMVP		0.54
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1801253; hg19: chr10-115805056; COSMIC: COSV65167813;