12-1754459-A-G

Variant names:

• chr12-1754459-A-G
• rs12298275
• NM_024551.3:c.116A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_024551.3(ADIPOR2):​c.116A>G​(p.Gln39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,613,438 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (46 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (39 hom.)
• Consequence: ADIPOR2 NM_024551.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028038323).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0122 (1858/152236) while in subpopulation AFR AF = 0.043 (1783/41512). AF 95% confidence interval is 0.0413. There are 46 homozygotes in GnomAd4. There are 890 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1858 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024551.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOR2	NM_024551.3	MANE Select	c.116A>G	p.Gln39Arg	missense	Exon 2 of 8	NP_078827.2
	ADIPOR2	NM_001375363.1		c.116A>G	p.Gln39Arg	missense	Exon 2 of 9	NP_001362292.1
	ADIPOR2	NM_001375364.1		c.116A>G	p.Gln39Arg	missense	Exon 3 of 9	NP_001362293.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOR2	ENST00000357103.5	TSL:1 MANE Select	c.116A>G	p.Gln39Arg	missense	Exon 2 of 8	ENSP00000349616.4
	ADIPOR2	ENST00000537545.1	TSL:3	n.346A>G		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1856 AN: 152118 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00623

GnomAD2 exomes AF: 0.00310 AC: 776 AN: 250532 AF XY: 0.00233

Gnomad AFR exome AF: 0.0426

Gnomad AMR exome AF: 0.00208

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00117 AC: 1715 AN: 1461202 Hom.: 39 Cov.: 30 AF XY: 0.00102 AC XY: 739 AN XY: 726860

African (AFR) AF: 0.0417 AC: 1395 AN: 33450

American (AMR) AF: 0.00246 AC: 110 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86104

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5766

European-Non Finnish (NFE) AF: 0.0000234 AC: 26 AN: 1111688

Other (OTH) AF: 0.00285 AC: 172 AN: 60364

GnomAD4 genome AF: 0.0122 AC: 1858 AN: 152236 Hom.: 46 Cov.: 32 AF XY: 0.0120 AC XY: 890 AN XY: 74448

African (AFR) AF: 0.0430 AC: 1783 AN: 41512

American (AMR) AF: 0.00360 AC: 55 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68024

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.00463 Hom.: 40

Bravo AF: 0.0138

ESP6500AA AF: 0.0409 AC: 180

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00371 AC: 450

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.55	D
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.4
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.055
Sift	Benign	0.51	T
Sift4G	Benign	0.46	T
Polyphen		0.10	B
Vest4		0.095
MVP		0.46
MPC		0.92
ClinPred		0.0034	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.036
gMVP		0.21
Mutation Taster		=97/3	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: rs12298275; hg19: chr12-1863625; COSMIC: COSV99072329; COSMIC: COSV99072329;