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GeneBe

rs4994

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000025.3(ADRB3):c.190T>C(p.Trp64Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0927 in 152152 control chromosomes in the gnomAD Genomes database, including 761 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.093 ( 761 hom., cov: 33)
Exomes 𝑓: 0.11 ( 1769 hom. )

Consequence

ADRB3
NM_000025.3 missense

Scores

1
17

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 1.05

Links

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=8.1804395E-4).
BP6
?
Variant 8-37966280-A-G is Benign according to our data. Variant chr8-37966280-A-G is described in ClinVar as [Benign]. Clinvar id is 17741.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADRB3NM_000025.3 linkuse as main transcriptc.190T>C p.Trp64Arg missense_variant 1/2 ENST00000345060.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADRB3ENST00000345060.5 linkuse as main transcriptc.190T>C p.Trp64Arg missense_variant 1/21 NM_000025.3 P1
ADRB3ENST00000520341.2 linkuse as main transcriptn.318T>C non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.0927
AC:
14099
AN:
152152
Hom.:
761
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.104
Gnomad AMI
AF:
0.0154
Gnomad AMR
AF:
0.137
Gnomad ASJ
AF:
0.0487
Gnomad EAS
AF:
0.144
Gnomad SAS
AF:
0.131
Gnomad FIN
AF:
0.0806
Gnomad MID
AF:
0.0796
Gnomad NFE
AF:
0.0745
Gnomad OTH
AF:
0.0847
GnomAD3 exomes
AF:
0.106
AC:
26242
AN:
247172
Hom.:
1769
AF XY:
0.103
AC XY:
13824
AN XY:
134230
show subpopulations
Gnomad AFR exome
AF:
0.107
Gnomad AMR exome
AF:
0.205
Gnomad ASJ exome
AF:
0.0482
Gnomad EAS exome
AF:
0.142
Gnomad SAS exome
AF:
0.128
Gnomad FIN exome
AF:
0.0791
Gnomad NFE exome
AF:
0.0742
Gnomad OTH exome
AF:
0.0967
GnomAD4 exome
AF:
0.0880
AC:
128533
AN:
1461300
Hom.:
6363
AF XY:
0.0882
AC XY:
64153
AN XY:
726968
show subpopulations
Gnomad4 AFR exome
AF:
0.106
Gnomad4 AMR exome
AF:
0.197
Gnomad4 ASJ exome
AF:
0.0499
Gnomad4 EAS exome
AF:
0.165
Gnomad4 SAS exome
AF:
0.128
Gnomad4 FIN exome
AF:
0.0826
Gnomad4 NFE exome
AF:
0.0783
Gnomad4 OTH exome
AF:
0.0895
Alfa
AF:
0.0759
Hom.:
930
Bravo
AF:
0.0992
TwinsUK
AF:
0.0720
AC:
267
ALSPAC
AF:
0.0758
AC:
292
ESP6500AA
AF:
0.106
AC:
468
ESP6500EA
AF:
0.0756
AC:
649
ExAC
AF:
0.102
AC:
12436
Asia WGS
AF:
0.144
AC:
506
AN:
3478
EpiCase
AF:
0.0700
EpiControl
AF:
0.0707

ClinVar

Significance: Benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 09, 2021This variant is associated with the following publications: (PMID: 9080262, 29670643, 22774474, 11380082, 21529759, 23729572, 21289629, 21358132, 20008926, 20069060, 11564599, 17225053, 19553224, 22550477, 19133996, 21285172, 21034552, 19080138, 7487991, 28456594, 23968135, 20078877, 23032405) -
Obesity Other:1
risk factor, no assertion criteria providedliterature onlyOMIMOct 01, 2004- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.052
BayesDel_addAF
Benign
-0.75
T
BayesDel_noAF
Benign
-0.70
Cadd
Benign
18
Dann
Benign
0.44
DEOGEN2
Benign
0.044
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.094
N
LIST_S2
Benign
0.39
T
MetaRNN
Benign
0.00082
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-2.9
N
MutationTaster
Benign
1.0
P
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
6.1
N
REVEL
Benign
0.12
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.019
MutPred
0.23
Gain of methylation at W64 (P = 0.0847);
MPC
1.4
ClinPred
0.0028
T
GERP RS
2.4
Varity_R
0.11
gMVP
0.40

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: rs4994; hg19: chr8-37823798; COSMIC: COSV61461710; API