10-114045197-C-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_000684.3(ADRB1):c.1065C>A(p.Pro355=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,598,152 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (8 hom.)
• Consequence: ADRB1 NM_000684.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.246

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 10-114045197-C-A is Benign according to our data. Variant chr10-114045197-C-A is described in ClinVar as [Benign]. Clinvar id is 789895.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.246 with no splicing effect.
• BS2: High AC in GnomAd at 248 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRB1	NM_000684.3	c.1065C>A	p.Pro355=	synonymous_variant	1/1	ENST00000369295.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRB1	ENST00000369295.4	c.1065C>A	p.Pro355=	synonymous_variant	1/1		NM_000684.3	P1

Frequencies

GnomAD3 genomes AF: 0.00164 AC: 248 AN: 150768 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000774

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00782

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000100

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.00290

GnomAD3 exomes AF: 0.00198 AC: 471 AN: 237762 Hom.: 1 AF XY: 0.00213 AC XY: 278 AN XY: 130236

Gnomad AFR exome AF: 0.000413

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00601

Gnomad EAS exome AF: 0.0000576

Gnomad SAS exome AF: 0.00241

Gnomad FIN exome AF: 0.0000470

Gnomad NFE exome AF: 0.00261

Gnomad OTH exome AF: 0.00174

GnomAD4 exome AF: 0.00304 AC: 4400 AN: 1447276 Hom.: 8 Cov.: 31 AF XY: 0.00299 AC XY: 2152 AN XY: 720062

Gnomad4 AFR exome AF: 0.000305

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.00579

Gnomad4 EAS exome AF: 0.0000258

Gnomad4 SAS exome AF: 0.00283

Gnomad4 FIN exome AF: 0.000115

Gnomad4 NFE exome AF: 0.00341

Gnomad4 OTH exome AF: 0.00280

GnomAD4 genome AF: 0.00164 AC: 248 AN: 150876 Hom.: 1 Cov.: 32 AF XY: 0.00142 AC XY: 105 AN XY: 73696

Gnomad4 AFR AF: 0.000772

Gnomad4 AMR AF: 0.00125

Gnomad4 ASJ AF: 0.00782

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000100

Gnomad4 NFE AF: 0.00231

Gnomad4 OTH AF: 0.00287

Alfa AF: 0.00246 Hom.: 0

Bravo AF: 0.00188

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

Jun 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	5.9
Dann	Benign	0.90

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: rs141633952; hg19: chr10-115804956;