8-37964944-T-TA

Position:

• chr8-37964944-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000025.3(ADRB3):​c.1205+320_1205+321insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 243,232 control chromosomes in the GnomAD database, including 633 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.090 (630 hom., cov: 31)
  • Exomes 𝑓: 0.084 (3 hom.)
• Consequence: ADRB3 NM_000025.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.114

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 -10 ACMG points.

• BP6: Variant 8-37964944-T-TA is Benign according to our data. Variant chr8-37964944-T-TA is described in ClinVar as [Benign]. Clinvar id is 1288105.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRB3	NM_000025.3	c.1205+320_1205+321insT		intron_variant		ENST00000345060.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRB3	ENST00000345060.5	c.1205+320_1205+321insT		intron_variant		1	NM_000025.3	P1
ADRB3	ENST00000520341.2			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0896 AC: 12931 AN: 144390 Hom.: 630 Cov.: 31

Gnomad AFR AF: 0.0977

Gnomad AMI AF: 0.0293

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.0888

Gnomad NFE AF: 0.0750

Gnomad OTH AF: 0.0822

GnomAD4 exome AF: 0.0836 AC: 8259 AN: 98780 Hom.: 3 Cov.: 0 AF XY: 0.0829 AC XY: 4091 AN XY: 49336

Gnomad4 AFR exome AF: 0.0958

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.0538

Gnomad4 EAS exome AF: 0.152

Gnomad4 SAS exome AF: 0.0939

Gnomad4 FIN exome AF: 0.0710

Gnomad4 NFE exome AF: 0.0761

Gnomad4 OTH exome AF: 0.0811

GnomAD4 genome AF: 0.0897 AC: 12953 AN: 144452 Hom.: 630 Cov.: 31 AF XY: 0.0906 AC XY: 6356 AN XY: 70158

Gnomad4 AFR AF: 0.0980

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0602

Gnomad4 NFE AF: 0.0750

Gnomad4 OTH AF: 0.0821

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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs762791184; hg19: chr8-37822462;