NM_000684.3:c.1199G>C

Variant names:

• chr10-114045331-G-C
• rs171170
• NM_000684.3:c.1199G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000684.3(ADRB1):​c.1199G>C​(p.Arg400Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000729 in 1,372,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R400W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: ADRB1 NM_000684.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.68
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34332693).

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.1199G>C	p.Arg400Pro	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.1199G>C	p.Arg400Pro	missense	Exon 1 of 1	ENSP00000358301.2	P08588

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1372154 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 682764

African (AFR) AF: 0.00 AC: 0 AN: 28594

American (AMR) AF: 0.00 AC: 0 AN: 36954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23250

East Asian (EAS) AF: 0.00 AC: 0 AN: 32036

South Asian (SAS) AF: 0.00 AC: 0 AN: 77754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5400

European-Non Finnish (NFE) AF: 9.40e-7 AC: 1 AN: 1063646

Other (OTH) AF: 0.00 AC: 0 AN: 55506

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	23
DANN	Benign	0.97
Eigen	Benign	0.13
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.0	T
PhyloP100		5.7
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.073
Sift	Uncertain	0.027	D
Sift4G	Benign	0.082	T
Vest4		0.31
MutPred		0.32		Gain of glycosylation at R400 (P = 0.0242)
MVP		0.56
ClinPred		0.84	D
GERP RS		4.2
gMVP		0.62
Mutation Taster		=62/38	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: rs171170; hg19: chr10-115805090;