rs1801253

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000684.3(ADRB1):​c.1165G>A​(p.Gly389Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G389V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADRB1 NM_000684.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059390485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB1	NM_000684.3	c.1165G>A	p.Gly389Arg	missense_variant	Exon 1 of 1	ENST00000369295.4	NP_000675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRB1	ENST00000369295.4	c.1165G>A	p.Gly389Arg	missense_variant	Exon 1 of 1	6	NM_000684.3	ENSP00000358301.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1427478 Hom.: 0 Cov.: 58 AF XY: 0.00 AC XY: 0 AN XY: 710218

African (AFR) AF: 0.00 AC: 0 AN: 31344

American (AMR) AF: 0.00 AC: 0 AN: 41488

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25256

East Asian (EAS) AF: 0.00 AC: 0 AN: 36394

South Asian (SAS) AF: 0.00 AC: 0 AN: 83036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094130

Other (OTH) AF: 0.00 AC: 0 AN: 58674

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.96
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.28	N
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.0
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	3.2	N
REVEL	Benign	0.071
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.055
MutPred		0.32		Gain of MoRF binding (P = 0.02);
MVP		0.51
ClinPred		0.48	T
GERP RS		1.7
gMVP		0.54
Mutation Taster		=96/4	polymorphism

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;