rs730031

Variant names:

• chr12-1786042-C-T
• rs730031
• NM_024551.3:c.1131C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_024551.3(ADIPOR2):​c.1131C>T​(p.Gly377Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,613,982 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0061 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (10 hom.)
• Consequence: ADIPOR2 NM_024551.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.30
• 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 12-1786042-C-T is Benign according to our data. Variant chr12-1786042-C-T is described in ClinVar as Benign. ClinVar VariationId is 785390.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.3 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00614 (934/152144) while in subpopulation AFR AF = 0.0214 (887/41484). AF 95% confidence interval is 0.0202. There are 10 homozygotes in GnomAd4. There are 438 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 934 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOR2	NM_024551.3	MANE Select	c.1131C>T	p.Gly377Gly	synonymous	Exon 8 of 8	NP_078827.2
	ADIPOR2	NM_001375363.1		c.1230C>T	p.Gly410Gly	synonymous	Exon 9 of 9	NP_001362292.1
	ADIPOR2	NM_001375364.1		c.1131C>T	p.Gly377Gly	synonymous	Exon 9 of 9	NP_001362293.1	Q86V24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOR2	ENST00000357103.5	TSL:1 MANE Select	c.1131C>T	p.Gly377Gly	synonymous	Exon 8 of 8	ENSP00000349616.4	Q86V24
	ADIPOR2	ENST00000878990.1		c.1314C>T	p.Gly438Gly	synonymous	Exon 10 of 10	ENSP00000549049.1
	ADIPOR2	ENST00000878964.1		c.1236C>T	p.Gly412Gly	synonymous	Exon 9 of 9	ENSP00000549023.1

Frequencies

GnomAD3 genomes AF: 0.00614 AC: 933 AN: 152026 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00622

GnomAD2 exomes AF: 0.00156 AC: 392 AN: 251416 AF XY: 0.00108

Gnomad AFR exome AF: 0.0214

Gnomad AMR exome AF: 0.000925

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000605 AC: 884 AN: 1461838 Hom.: 10 Cov.: 31 AF XY: 0.000505 AC XY: 367 AN XY: 727230

African (AFR) AF: 0.0218 AC: 729 AN: 33480

American (AMR) AF: 0.000984 AC: 44 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000697 AC: 4 AN: 5740

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1112000

Other (OTH) AF: 0.00123 AC: 74 AN: 60388

GnomAD4 genome AF: 0.00614 AC: 934 AN: 152144 Hom.: 10 Cov.: 32 AF XY: 0.00589 AC XY: 438 AN XY: 74384

African (AFR) AF: 0.0214 AC: 887 AN: 41484

American (AMR) AF: 0.00176 AC: 27 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67996

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00311 Hom.: 2

Bravo AF: 0.00671

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.2
DANN	Benign	0.54
PhyloP100		-2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs730031; hg19: chr12-1895208;