chr10-114045070-G-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_000684.3(ADRB1):āc.938G>Cā(p.Arg313Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000183 in 1,422,560 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000027 ( 0 hom., cov: 32)
Exomes š: 0.000017 ( 0 hom. )
Consequence
ADRB1
NM_000684.3 missense
NM_000684.3 missense
Scores
2
11
3
Clinical Significance
Conservation
PhyloP100: 3.94
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 22 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADRB1 | NM_000684.3 | c.938G>C | p.Arg313Pro | missense_variant | 1/1 | ENST00000369295.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADRB1 | ENST00000369295.4 | c.938G>C | p.Arg313Pro | missense_variant | 1/1 | NM_000684.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000267 AC: 4AN: 149966Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000297 AC: 3AN: 100996Hom.: 0 AF XY: 0.0000526 AC XY: 3AN XY: 57070
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GnomAD4 exome AF: 0.0000173 AC: 22AN: 1272488Hom.: 0 Cov.: 30 AF XY: 0.0000223 AC XY: 14AN XY: 627752
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GnomAD4 genome AF: 0.0000267 AC: 4AN: 150072Hom.: 0 Cov.: 32 AF XY: 0.0000273 AC XY: 2AN XY: 73264
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 20, 2023 | The c.938G>C (p.R313P) alteration is located in exon 1 (coding exon 1) of the ADRB1 gene. This alteration results from a G to C substitution at nucleotide position 938, causing the arginine (R) at amino acid position 313 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Vest4
MutPred
Gain of glycosylation at R313 (P = 0.0046);
MVP
ClinPred
D
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at