chr8-37964944-T-TAA

Variant names:

• chr8-37964944-T-TAA
• rs762791184
• NM_000025.3:c.1205+319_1205+320dupTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_000025.3(ADRB3):​c.1205+319_1205+320dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 243,420 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0036 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0019 (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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB3	NM_000025.3	c.1205+319_1205+320dupTT		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+319_1205+320dupTT		intron_variant	Intron 1 of 1	1	NM_000025.3	ENSP00000343782.3
ENSG00000285880	ENST00000647937.1	c.689+319_689+320dupTT		intron_variant	Intron 1 of 1			ENSP00000497740.1
ADRB3	ENST00000520341.2	n.*28_*29dupTT		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 508 AN: 144430 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000203

Gnomad SAS AF: 0.00198

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000381

Gnomad OTH AF: 0.00300

GnomAD4 exome AF: 0.00186 AC: 184 AN: 98928 Hom.: 0 Cov.: 0 AF XY: 0.00184 AC XY: 91 AN XY: 49440

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

African (AFR) AF: 0.0101 AC: 31 AN: 3080

American (AMR) AF: 0.00387 AC: 10 AN: 2582

Ashkenazi Jewish (ASJ) AF: 0.000802 AC: 3 AN: 3740

East Asian (EAS) AF: 0.00270 AC: 20 AN: 7400

South Asian (SAS) AF: 0.00166 AC: 4 AN: 2408

European-Finnish (FIN) AF: 0.000885 AC: 5 AN: 5650

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 562

European-Non Finnish (NFE) AF: 0.00144 AC: 96 AN: 66588

Other (OTH) AF: 0.00217 AC: 15 AN: 6918

⚠️ 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 AF: 0.00359 AC: 519 AN: 144492 Hom.: 3 Cov.: 31 AF XY: 0.00338 AC XY: 237 AN XY: 70182

African (AFR) AF: 0.0116 AC: 456 AN: 39378

American (AMR) AF: 0.00151 AC: 22 AN: 14614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3362

East Asian (EAS) AF: 0.000203 AC: 1 AN: 4920

South Asian (SAS) AF: 0.00199 AC: 9 AN: 4532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.000381 AC: 25 AN: 65636

Other (OTH) AF: 0.00298 AC: 6 AN: 2012

Alfa AF: 0.0000701 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;