rs9805042

chr12-1784004-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_024551.3(ADIPOR2):c.963C>T(p.Tyr321=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,613,196 control chromosomes in the GnomAD database, including 21,924 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (5732 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16192 hom.)
• Consequence: ADIPOR2 NM_024551.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177

Genes affected

ADIPOR2 (HGNC:24041): (adiponectin receptor 2) The adiponectin receptors, ADIPOR1 (MIM 607945) and ADIPOR2, serve as receptors for globular and full-length adiponectin (MIM 605441) and mediate increased AMPK (see MIM 602739) and PPAR-alpha (PPARA; MIM 170998) ligand activities, as well as fatty acid oxidation and glucose uptake by adiponectin (Yamauchi et al., 2003 [PubMed 12802337]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.177 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADIPOR2	NM_024551.3	c.963C>T	p.Tyr321=	synonymous_variant	7/8	ENST00000357103.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADIPOR2	ENST00000357103.5	c.963C>T	p.Tyr321=	synonymous_variant	7/8	1	NM_024551.3	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34067 AN: 151986 Hom.: 5720 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.208

GnomAD3 exomes AF: 0.144 AC: 36042 AN: 250636 Hom.: 3708 AF XY: 0.140 AC XY: 18925 AN XY: 135454

Gnomad AFR exome AF: 0.484

Gnomad AMR exome AF: 0.0785

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.0930

Gnomad SAS exome AF: 0.146

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.136 AC: 199069 AN: 1461092 Hom.: 16192 Cov.: 31 AF XY: 0.136 AC XY: 98495 AN XY: 726844

Gnomad4 AFR exome AF: 0.487

Gnomad4 AMR exome AF: 0.0835

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.0740

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.130

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.224 AC: 34117 AN: 152104 Hom.: 5732 Cov.: 32 AF XY: 0.221 AC XY: 16403 AN XY: 74356

Gnomad4 AFR AF: 0.475

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.207

Alfa AF: 0.182 Hom.: 2216

Bravo AF: 0.235

Asia WGS AF: 0.160 AC: 556 AN: 3478

EpiCase AF: 0.133

EpiControl AF: 0.126

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	5.6
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs9805042; hg19: chr12-1893170; COSMIC: COSV63945740; COSMIC: COSV63945740;