12-1780116-T-G

Variant names:

• chr12-1780116-T-G
• rs4140993
• NM_024551.3:c.464-335T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024551.3(ADIPOR2):​c.464-335T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 183,788 control chromosomes in the GnomAD database, including 661 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 0.057 (633 hom., cov: 32)
  • Exomes 𝑓: 0.018 (28 hom.)
• Consequence: ADIPOR2 NM_024551.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOR2	NM_024551.3	c.464-335T>G		intron_variant	Intron 4 of 7	ENST00000357103.5	NP_078827.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADIPOR2	ENST00000357103.5	c.464-335T>G		intron_variant	Intron 4 of 7	1	NM_024551.3	ENSP00000349616.4
ADIPOR2	ENST00000535774.1	n.421-335T>G		intron_variant	Intron 2 of 2	4
ADIPOR2	ENST00000537190.1	n.-32T>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0572 AC: 8712 AN: 152178 Hom.: 635 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.0800

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.00282

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00494

Gnomad OTH AF: 0.0512

GnomAD4 exome AF: 0.0183 AC: 575 AN: 31492 Hom.: 28 Cov.: 0 AF XY: 0.0186 AC XY: 302 AN XY: 16204

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.0186

Gnomad4 ASJ exome AF: 0.0369

Gnomad4 EAS exome AF: 0.0480

Gnomad4 SAS exome AF: 0.0595

Gnomad4 FIN exome AF: 0.00392

Gnomad4 NFE exome AF: 0.00440

Gnomad4 OTH exome AF: 0.0412

GnomAD4 genome AF: 0.0574 AC: 8737 AN: 152296 Hom.: 633 Cov.: 32 AF XY: 0.0584 AC XY: 4351 AN XY: 74488

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.0316

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.0803

Gnomad4 SAS AF: 0.0814

Gnomad4 FIN AF: 0.00282

Gnomad4 NFE AF: 0.00494

Gnomad4 OTH AF: 0.0521

Alfa AF: 0.0123 Hom.: 81

Bravo AF: 0.0616

Asia WGS AF: 0.101 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs4140993; hg19: chr12-1889282;