12-1774523-T-G

Variant names:

• chr12-1774523-T-G
• rs11614639
• NM_024551.3:c.291+1562T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024551.3(ADIPOR2):​c.291+1562T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,018 control chromosomes in the GnomAD database, including 16,043 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 0.46 (16043 hom., cov: 32)
• Consequence: ADIPOR2 NM_024551.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.581
• Publications: 7 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 (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOR2	NM_024551.3	c.291+1562T>G		intron_variant	Intron 3 of 7	ENST00000357103.5	NP_078827.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADIPOR2	ENST00000357103.5	c.291+1562T>G		intron_variant	Intron 3 of 7	1	NM_024551.3	ENSP00000349616.4
ADIPOR2	ENST00000535774.1	n.248+1562T>G		intron_variant	Intron 1 of 2	4
ADIPOR2	ENST00000543456.1	n.372+1562T>G		intron_variant	Intron 2 of 2	3
ADIPOR2	ENST00000544470.1	n.39+1562T>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69384 AN: 151900 Hom.: 16031 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.495

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.457 AC: 69435 AN: 152018 Hom.: 16043 Cov.: 32 AF XY: 0.460 AC XY: 34204 AN XY: 74302

African (AFR) AF: 0.427 AC: 17697 AN: 41442

American (AMR) AF: 0.567 AC: 8664 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1540 AN: 3468

East Asian (EAS) AF: 0.517 AC: 2669 AN: 5158

South Asian (SAS) AF: 0.474 AC: 2284 AN: 4816

European-Finnish (FIN) AF: 0.468 AC: 4949 AN: 10576

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30094 AN: 67956

Other (OTH) AF: 0.494 AC: 1044 AN: 2114

Alfa AF: 0.444 Hom.: 3137

Bravo AF: 0.467

Asia WGS AF: 0.490 AC: 1701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.58
Mutation Taster		=99/1	polymorphism (auto)

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: rs11614639; hg19: chr12-1883689;