chr8-37964944-T-TAAA

Variant names:

• chr8-37964944-T-TAAA
• rs762791184
• NM_000025.3:c.1205+318_1205+320dupTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000025.3(ADRB3):​c.1205+318_1205+320dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000303 in 99,092 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: ADRB3 NM_000025.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 0 publications found

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]

ENSG00000285880 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB3	NM_000025.3	c.1205+318_1205+320dupTTT		intron_variant	Intron 1 of 1	ENST00000345060.5	NP_000016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRB3	ENST00000345060.5	c.1205+318_1205+320dupTTT		intron_variant	Intron 1 of 1	1	NM_000025.3	ENSP00000343782.3
ENSG00000285880	ENST00000647937.1	c.689+318_689+320dupTTT		intron_variant	Intron 1 of 1			ENSP00000497740.1
ADRB3	ENST00000520341.2	n.*27_*29dupTTT		downstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000303 AC: 3 AN: 99092 Hom.: 0 Cov.: 0 AF XY: 0.0000202 AC XY: 1 AN XY: 49516

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 3082

American (AMR) AF: 0.00 AC: 0 AN: 2586

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3748

East Asian (EAS) AF: 0.000135 AC: 1 AN: 7418

South Asian (SAS) AF: 0.00 AC: 0 AN: 2412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5656

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 566

European-Non Finnish (NFE) AF: 0.0000300 AC: 2 AN: 66692

Other (OTH) AF: 0.00 AC: 0 AN: 6932

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 9

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs762791184; hg19: chr8-37822462;