rs1801252

Variant names:

• chr10-114044277-A-G
• rs1801252
• NM_000684.3:c.145A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000684.3(ADRB1):​c.145A>G​(p.Ser49Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,542,848 control chromosomes in the GnomAD database, including 15,863 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2334 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13529 hom.)
• Consequence: ADRB1 NM_000684.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3 O:1
• Conservation: PhyloP100: -0.0190
• Publications: 314 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041767657).
• BP6: Variant 10-114044277-A-G is Benign according to our data. Variant chr10-114044277-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 17747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 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.145A>G	p.Ser49Gly	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.145A>G	p.Ser49Gly	missense	Exon 1 of 1	ENSP00000358301.2	P08588

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25425 AN: 151864 Hom.: 2319 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.150

GnomAD2 exomes AF: 0.154 AC: 25769 AN: 167050 AF XY: 0.145

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.285

Gnomad ASJ exome AF: 0.0778

Gnomad EAS exome AF: 0.140

Gnomad FIN exome AF: 0.175

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.134 AC: 186879 AN: 1390870 Hom.: 13529 Cov.: 31 AF XY: 0.133 AC XY: 92056 AN XY: 691118

African (AFR) AF: 0.220 AC: 6468 AN: 29426

American (AMR) AF: 0.275 AC: 9570 AN: 34776

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 2099 AN: 24198

East Asian (EAS) AF: 0.145 AC: 5047 AN: 34878

South Asian (SAS) AF: 0.135 AC: 10713 AN: 79578

European-Finnish (FIN) AF: 0.178 AC: 6633 AN: 37266

Middle Eastern (MID) AF: 0.0874 AC: 468 AN: 5354

European-Non Finnish (NFE) AF: 0.127 AC: 137927 AN: 1087794

Other (OTH) AF: 0.138 AC: 7954 AN: 57600

GnomAD4 genome AF: 0.168 AC: 25487 AN: 151978 Hom.: 2334 Cov.: 32 AF XY: 0.168 AC XY: 12513 AN XY: 74294

African (AFR) AF: 0.228 AC: 9447 AN: 41484

American (AMR) AF: 0.216 AC: 3296 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0905 AC: 314 AN: 3468

East Asian (EAS) AF: 0.147 AC: 756 AN: 5140

South Asian (SAS) AF: 0.124 AC: 598 AN: 4820

European-Finnish (FIN) AF: 0.175 AC: 1848 AN: 10576

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.130 AC: 8817 AN: 67902

Other (OTH) AF: 0.149 AC: 314 AN: 2104

Alfa AF: 0.138 Hom.: 985

Bravo AF: 0.175

TwinsUK AF: 0.127 AC: 472

ALSPAC AF: 0.141 AC: 545

ESP6500AA AF: 0.194 AC: 828

ESP6500EA AF: 0.108 AC: 905

ExAC AF: 0.145 AC: 17331

Asia WGS AF: 0.159 AC: 549 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	ADRB1-related disorder (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	-	Resting heart rate (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.9
DANN	Benign	0.12
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0050	N
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.019
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.040
Sift	Benign	0.81	T
Sift4G	Benign	0.42	T
Vest4		0.011
ClinPred		0.0032	T
GERP RS		1.5
PromoterAI		0.052	Neutral
gMVP		0.13
Mutation Taster		=99/1	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: rs1801252; hg19: chr10-115804036; COSMIC: COSV65168046;