8-37964335-T-C

Position:

• chr8-37964335-T-C

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.1206-96A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0854 in 1,143,280 control chromosomes in the GnomAD database, including 5,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.091 (747 hom., cov: 32)
  • Exomes 𝑓: 0.084 (4269 hom.)
• Consequence: ADRB3 NM_000025.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.198

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=-0.83).
• BP6: Variant 8-37964335-T-C is Benign according to our data. Variant chr8-37964335-T-C is described in ClinVar as [Benign]. Clinvar id is 1244998.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRB3	NM_000025.3	c.1206-96A>G		intron_variant		ENST00000345060.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRB3	ENST00000345060.5	c.1206-96A>G		intron_variant		1	NM_000025.3	P1

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13835 AN: 151866 Hom.: 738 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0361

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.0815

GnomAD4 exome AF: 0.0844 AC: 83709 AN: 991294 Hom.: 4269 AF XY: 0.0847 AC XY: 43019 AN XY: 507970

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.0367

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.0816

Gnomad4 NFE exome AF: 0.0727

Gnomad4 OTH exome AF: 0.0831

GnomAD4 genome AF: 0.0913 AC: 13880 AN: 151986 Hom.: 747 Cov.: 32 AF XY: 0.0934 AC XY: 6940 AN XY: 74304

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0361

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0807

Gnomad4 NFE AF: 0.0732

Gnomad4 OTH AF: 0.0811

Alfa AF: 0.0354 Hom.: 15

Bravo AF: 0.0975

Asia WGS AF: 0.142 AC: 497 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	-0.83
CADD	Benign	3.2
DANN	Benign	0.62

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: rs2071493; hg19: chr8-37821853; COSMIC: COSV61461636; COSMIC: COSV61461636;