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GeneBe

10-114044447-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000684.3(ADRB1):c.315G>T(p.Leu105=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00564 in 1,613,128 control chromosomes in the GnomAD database, including 467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.030 ( 252 hom., cov: 32)
Exomes 𝑓: 0.0031 ( 215 hom. )

Consequence

ADRB1
NM_000684.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.45
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-114044447-G-T is Benign according to our data. Variant chr10-114044447-G-T is described in ClinVar as [Benign]. Clinvar id is 776545.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=3.45 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADRB1NM_000684.3 linkuse as main transcriptc.315G>T p.Leu105= synonymous_variant 1/1 ENST00000369295.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADRB1ENST00000369295.4 linkuse as main transcriptc.315G>T p.Leu105= synonymous_variant 1/1 NM_000684.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0296
AC:
4505
AN:
152168
Hom.:
250
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.103
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00968
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000441
Gnomad OTH
AF:
0.0272
GnomAD3 exomes
AF:
0.00733
AC:
1834
AN:
250066
Hom.:
72
AF XY:
0.00527
AC XY:
714
AN XY:
135410
show subpopulations
Gnomad AFR exome
AF:
0.102
Gnomad AMR exome
AF:
0.00388
Gnomad ASJ exome
AF:
0.0000994
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000282
Gnomad OTH exome
AF:
0.00360
GnomAD4 exome
AF:
0.00314
AC:
4583
AN:
1460842
Hom.:
215
Cov.:
32
AF XY:
0.00272
AC XY:
1978
AN XY:
726786
show subpopulations
Gnomad4 AFR exome
AF:
0.112
Gnomad4 AMR exome
AF:
0.00490
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000220
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000151
Gnomad4 OTH exome
AF:
0.00659
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0296
AC:
4514
AN:
152286
Hom.:
252
Cov.:
32
AF XY:
0.0280
AC XY:
2083
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.103
Gnomad4 AMR
AF:
0.00967
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000441
Gnomad4 OTH
AF:
0.0269
Alfa
AF:
0.0155
Hom.:
55
Bravo
AF:
0.0347
Asia WGS
AF:
0.00433
AC:
15
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000296

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
Cadd
Benign
9.6
Dann
Benign
0.74

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: rs7921133; hg19: chr10-115804206; COSMIC: COSV65168034; API