rs180897

Variant names:

• chr10-114045159-G-A
• rs180897
• NM_000684.3:c.1027G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-114045159-G-A
• chr10-114045159-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000684.3(ADRB1):​c.1027G>A​(p.Ala343Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADRB1 NM_000684.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.36
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRB1	NM_000684.3	MANE Select	c.1027G>A	p.Ala343Thr	missense	Exon 1 of 1	NP_000675.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRB1	ENST00000369295.4	TSL:6 MANE Select	c.1027G>A	p.Ala343Thr	missense	Exon 1 of 1	ENSP00000358301.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1445926 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719278

African (AFR) AF: 0.00 AC: 0 AN: 32744

American (AMR) AF: 0.00 AC: 0 AN: 42986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25794

East Asian (EAS) AF: 0.00 AC: 0 AN: 38598

South Asian (SAS) AF: 0.00 AC: 0 AN: 84378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104372

Other (OTH) AF: 0.00 AC: 0 AN: 59640

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	26
DANN	Uncertain	1.0
Eigen	Benign	0.0080
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Pathogenic	0.90	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.43	T
PhyloP100		6.4
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.17
Sift	Uncertain	0.014	D
Sift4G	Benign	0.14	T
Vest4		0.22
MutPred		0.51		Gain of methylation at K347 (P = 0.0583)
MVP		0.58
ClinPred		0.89	D
GERP RS		3.8
gMVP		0.53
Mutation Taster		=79/21	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: rs180897; hg19: chr10-115804918;