rs1801253

chr10-114045297-G-Achr10-114045297-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. 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. In-silico tool predicts a benign outcome for this variant. 11/17 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 same amino acid change has been previously reported as Benignin 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

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.059390485).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRB1	NM_000684.3	c.1165G>A	p.Gly389Arg	missense_variant	1/1	ENST00000369295.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRB1	ENST00000369295.4	c.1165G>A	p.Gly389Arg	missense_variant	1/1		NM_000684.3	P1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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
MutationTaster	Benign	1.0	N
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

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

LitVar

Other links and lift over

dbSNP: rs1801253; hg19: chr10-115805056;