chr12-1727646-G-A

Variant names:

• chr12-1727646-G-A
• rs4140992
• NM_024551.3:c.-86-26612G>A

Variant summary

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

The NM_024551.3(ADIPOR2):​c.-86-26612G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,582 control chromosomes in the GnomAD database, including 12,658 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 0.38 (12658 hom., cov: 29)
• Consequence: ADIPOR2 NM_024551.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOR2	NM_024551.3	c.-86-26612G>A		intron_variant	Intron 1 of 7	ENST00000357103.5	NP_078827.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADIPOR2	ENST00000357103.5	c.-86-26612G>A		intron_variant	Intron 1 of 7	1	NM_024551.3	ENSP00000349616.4
ADIPOR2	ENST00000537545.1	n.145-26612G>A		intron_variant	Intron 1 of 2	3
ADIPOR2	ENST00000540974.1	n.149-3079G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58008 AN: 151464 Hom.: 12657 Cov.: 29

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.383 AC: 58009 AN: 151582 Hom.: 12658 Cov.: 29 AF XY: 0.382 AC XY: 28278 AN XY: 74046

African (AFR) AF: 0.167 AC: 6893 AN: 41350

American (AMR) AF: 0.351 AC: 5335 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1525 AN: 3464

East Asian (EAS) AF: 0.396 AC: 2026 AN: 5118

South Asian (SAS) AF: 0.415 AC: 1985 AN: 4780

European-Finnish (FIN) AF: 0.469 AC: 4906 AN: 10464

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33915 AN: 67884

Other (OTH) AF: 0.364 AC: 766 AN: 2102

Alfa AF: 0.450 Hom.: 2730

Bravo AF: 0.362

Asia WGS AF: 0.365 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.75
PhyloP100		0.52
Mutation Taster		=100/0	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: rs4140992; hg19: chr12-1836812;