10-114044692-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP5BP4BS2

The NM_000684.3(ADRB1):​c.560C>T​(p.Ala187Val) variant causes a missense change. The variant allele was found at a frequency of 0.000122 in 1,612,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

ADRB1
NM_000684.3 missense

Scores

1
5
10

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.98
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PP5
Variant 10-114044692-C-T is Pathogenic according to our data. Variant chr10-114044692-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 691285.Status of the report is no_assertion_criteria_provided, 0 stars.
BP4
Computational evidence support a benign effect (MetaRNN=0.35386938). . Strength limited to SUPPORTING due to the PP5.
BS2
High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADRB1NM_000684.3 linkc.560C>T p.Ala187Val missense_variant Exon 1 of 1 ENST00000369295.4 NP_000675.1 P08588

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADRB1ENST00000369295.4 linkc.560C>T p.Ala187Val missense_variant Exon 1 of 1 6 NM_000684.3 ENSP00000358301.2 P08588

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000364
AC:
9
AN:
247054
Hom.:
0
AF XY:
0.0000448
AC XY:
6
AN XY:
134034
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000721
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000129
AC:
188
AN:
1460256
Hom.:
0
Cov.:
32
AF XY:
0.000127
AC XY:
92
AN XY:
726524
show subpopulations
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:
0.000165
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000141
Hom.:
0
Bravo
AF:
0.0000529
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

SHORT SLEEP, FAMILIAL NATURAL, 2 Pathogenic:1
Jun 18, 2024
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
25
DANN
Uncertain
1.0
Eigen
Benign
0.10
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.90
D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.35
T
MetaSVM
Benign
-1.0
T
PrimateAI
Pathogenic
0.90
D
PROVEAN
Uncertain
-3.3
D
REVEL
Benign
0.12
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.011
D
Vest4
0.55
MutPred
0.53
Loss of MoRF binding (P = 0.1604);
MVP
0.47
ClinPred
0.45
T
GERP RS
3.5
gMVP
0.81

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs776439595; hg19: chr10-115804451; API