rs34010966

Positions:

• chr1-202948219-G-C

Variant summary

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

The NM_015999.6(ADIPOR1):​c.258+85C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 1,101,718 control chromosomes in the GnomAD database, including 1,461 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 0.042 (176 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1285 hom.)
• Consequence: ADIPOR1 NM_015999.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686

Genes affected

ADIPOR1 (HGNC:24040): (adiponectin receptor 1) This gene encodes a protein which acts as a receptor for adiponectin, a hormone secreted by adipocytes which regulates fatty acid catabolism and glucose levels. Binding of adiponectin to the encoded protein results in activation of an AMP-activated kinase signaling pathway which affects levels of fatty acid oxidation and insulin sensitivity. A pseudogene of this gene is located on chromosome 14. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADIPOR1	NM_015999.6	c.258+85C>G		intron_variant		ENST00000340990.10	NP_057083.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADIPOR1	ENST00000340990.10	c.258+85C>G		intron_variant		1	NM_015999.6	ENSP00000341785	P1
ADIPOR1	ENST00000367254.7	c.258+85C>G		intron_variant		1		ENSP00000356223
ADIPOR1	ENST00000417068.5	c.258+85C>G		intron_variant		3		ENSP00000402178
ADIPOR1	ENST00000426229.1	c.258+85C>G		intron_variant		2		ENSP00000392946

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 6335 AN: 152080 Hom.: 172 Cov.: 32

Gnomad AFR AF: 0.0427

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.0375

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0294

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0371

Gnomad OTH AF: 0.0425

GnomAD4 exome AF: 0.0454 AC: 43092 AN: 949520 Hom.: 1285 AF XY: 0.0475 AC XY: 22703 AN XY: 478374

Gnomad4 AFR exome AF: 0.0447

Gnomad4 AMR exome AF: 0.0203

Gnomad4 ASJ exome AF: 0.0408

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.0334

Gnomad4 NFE exome AF: 0.0391

Gnomad4 OTH exome AF: 0.0473

GnomAD4 genome AF: 0.0417 AC: 6352 AN: 152198 Hom.: 176 Cov.: 32 AF XY: 0.0422 AC XY: 3137 AN XY: 74422

Gnomad4 AFR AF: 0.0431

Gnomad4 AMR AF: 0.0240

Gnomad4 ASJ AF: 0.0375

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0294

Gnomad4 NFE AF: 0.0371

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0385 Hom.: 21

Bravo AF: 0.0394

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs34010966; hg19: chr1-202917347; COSMIC: COSV61852220; COSMIC: COSV61852220;