rs4998

Positions:

• chr8-37963968-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000025.3(ADRB3):​c.*250G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 463,364 control chromosomes in the GnomAD database, including 2,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (750 hom., cov: 32)
  • Exomes 𝑓: 0.087 (1405 hom.)
• Consequence: ADRB3 NM_000025.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0130

Genes affected

ADRB3 (HGNC:288): (adrenoceptor beta 3) The protein encoded by this gene belongs to the family of beta adrenergic receptors, which mediate catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor is located mainly in the adipose tissue and is involved in the regulation of lipolysis and thermogenesis. Obesity and bodyweight-related disorders are correlated with certain polymorphisms in three subtypes of beta-adrenoceptor, among them, the ADRB3 gene.[provided by RefSeq, Oct 2019]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 8-37963968-C-G is Benign according to our data. Variant chr8-37963968-C-G is described in ClinVar as [Benign]. Clinvar id is 1264874.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 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
ADRB3	NM_000025.3	c.*250G>C		3_prime_UTR_variant	2/2	ENST00000345060.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRB3	ENST00000345060.5	c.*250G>C		3_prime_UTR_variant	2/2	1	NM_000025.3	P1

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13866 AN: 152130 Hom.: 742 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.0813

GnomAD4 exome AF: 0.0867 AC: 26973 AN: 311116 Hom.: 1405 Cov.: 2 AF XY: 0.0874 AC XY: 14310 AN XY: 163820

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.0347

Gnomad4 EAS exome AF: 0.168

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.0808

Gnomad4 NFE exome AF: 0.0718

Gnomad4 OTH exome AF: 0.0816

GnomAD4 genome AF: 0.0914 AC: 13910 AN: 152248 Hom.: 750 Cov.: 32 AF XY: 0.0935 AC XY: 6962 AN XY: 74442

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0807

Gnomad4 NFE AF: 0.0733

Gnomad4 OTH AF: 0.0809

Alfa AF: 0.0833 Hom.: 95

Bravo AF: 0.0974

Asia WGS AF: 0.142 AC: 498 AN: 3478

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

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.49

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: rs4998; hg19: chr8-37821486;