8-37964944-TAAAA-TAAA

Variant names:

• chr8-37964944-TA-T
• rs762791184
• NM_000025.3:c.1205+320delT

Variant summary

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

The NM_000025.3(ADRB3):​c.1205+320delT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0038 (0 hom., cov: 31)
  • Exomes 𝑓: 0.28 (0 hom.)
  • Failed GnomAD Quality Control
• 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 0 ACMG points.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00377 AC: 543 AN: 143902 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00537

Gnomad EAS AF: 0.00102

Gnomad SAS AF: 0.00264

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.00993

Gnomad NFE AF: 0.00358

Gnomad OTH AF: 0.00352

GnomAD4 exome AF: 0.280 AC: 26915 AN: 95976 Hom.: 0 Cov.: 0 AF XY: 0.281 AC XY: 13494 AN XY: 47944

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

African (AFR) AF: 0.277 AC: 828 AN: 2988

American (AMR) AF: 0.243 AC: 612 AN: 2522

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1099 AN: 3584

East Asian (EAS) AF: 0.243 AC: 1754 AN: 7230

South Asian (SAS) AF: 0.235 AC: 555 AN: 2358

European-Finnish (FIN) AF: 0.267 AC: 1468 AN: 5496

Middle Eastern (MID) AF: 0.296 AC: 162 AN: 548

European-Non Finnish (NFE) AF: 0.287 AC: 18491 AN: 64530

Other (OTH) AF: 0.290 AC: 1946 AN: 6720

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00379 AC: 545 AN: 143962 Hom.: 0 Cov.: 31 AF XY: 0.00419 AC XY: 293 AN XY: 69884

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

African (AFR) AF: 0.00175 AC: 69 AN: 39328

American (AMR) AF: 0.00288 AC: 42 AN: 14574

Ashkenazi Jewish (ASJ) AF: 0.00537 AC: 18 AN: 3350

East Asian (EAS) AF: 0.00122 AC: 6 AN: 4914

South Asian (SAS) AF: 0.00309 AC: 14 AN: 4528

European-Finnish (FIN) AF: 0.0174 AC: 152 AN: 8736

Middle Eastern (MID) AF: 0.0108 AC: 3 AN: 278

European-Non Finnish (NFE) AF: 0.00358 AC: 234 AN: 65364

Other (OTH) AF: 0.00350 AC: 7 AN: 2002

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs762791184; hg19: chr8-37822462;