10-114044146-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000684.3(ADRB1):c.14T>C(p.Val5Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,313,356 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0079 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (13 hom.)
• Consequence: ADRB1 NM_000684.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.176

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003424257).
• BP6: Variant 10-114044146-T-C is Benign according to our data. Variant chr10-114044146-T-C is described in ClinVar as [Benign]. Clinvar id is 717168.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00787 (1186/150768) while in subpopulation AFR AF= 0.0273 (1124/41178). AF 95% confidence interval is 0.026. There are 15 homozygotes in gnomad4. There are 532 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1181 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRB1	NM_000684.3	c.14T>C	p.Val5Ala	missense_variant	1/1	ENST00000369295.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRB1	ENST00000369295.4	c.14T>C	p.Val5Ala	missense_variant	1/1		NM_000684.3	P1

Frequencies

GnomAD3 genomes AF: 0.00784 AC: 1181 AN: 150662 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00277

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.00579

GnomAD4 exome AF: 0.000779 AC: 906 AN: 1162588 Hom.: 13 Cov.: 29 AF XY: 0.000696 AC XY: 391 AN XY: 561728

Gnomad4 AFR exome AF: 0.0293

Gnomad4 AMR exome AF: 0.00285

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: 0.000102

Gnomad4 OTH exome AF: 0.00219

GnomAD4 genome AF: 0.00787 AC: 1186 AN: 150768 Hom.: 15 Cov.: 32 AF XY: 0.00723 AC XY: 532 AN XY: 73630

Gnomad4 AFR AF: 0.0273

Gnomad4 AMR AF: 0.00277

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000104

Gnomad4 OTH AF: 0.00573

Alfa AF: 0.00472 Hom.: 1

ExAC AF: 0.000417 AC: 11

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	17
Dann	Benign	0.41
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.019	N
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.56	N
REVEL	Benign	0.054
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.082
MVP		0.13
ClinPred		0.071	T
GERP RS		1.2
gMVP		0.19

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

Other links and lift over

dbSNP: rs545019520; hg19: chr10-115803905;