rs7518457

Positions:

• chr1-202946408-A-G

Variant summary

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

The NM_015999.6(ADIPOR1):​c.430+31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00344 in 1,612,974 control chromosomes in the GnomAD database, including 173 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 0.017 (85 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (88 hom.)
• Consequence: ADIPOR1 NM_015999.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADIPOR1	NM_015999.6	c.430+31T>C		intron_variant		ENST00000340990.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADIPOR1	ENST00000340990.10	c.430+31T>C		intron_variant		1	NM_015999.6	P1
ADIPOR1	ENST00000367254.7	c.430+31T>C		intron_variant		1
ADIPOR1	ENST00000417068.5	c.430+31T>C		intron_variant		3
ADIPOR1	ENST00000426229.1	c.430+31T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0167 AC: 2545 AN: 152036 Hom.: 85 Cov.: 31

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00832

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00483 AC: 1206 AN: 249938 Hom.: 35 AF XY: 0.00364 AC XY: 492 AN XY: 135082

Gnomad AFR exome AF: 0.0576

Gnomad AMR exome AF: 0.00379

Gnomad ASJ exome AF: 0.0111

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00279

GnomAD4 exome AF: 0.00205 AC: 3001 AN: 1460820 Hom.: 88 Cov.: 30 AF XY: 0.00187 AC XY: 1359 AN XY: 726664

Gnomad4 AFR exome AF: 0.0622

Gnomad4 AMR exome AF: 0.00443

Gnomad4 ASJ exome AF: 0.0103

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000116

Gnomad4 OTH exome AF: 0.00471

GnomAD4 genome AF: 0.0168 AC: 2549 AN: 152154 Hom.: 85 Cov.: 31 AF XY: 0.0163 AC XY: 1215 AN XY: 74384

Gnomad4 AFR AF: 0.0561

Gnomad4 AMR AF: 0.00831

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00937 Hom.: 9

Bravo AF: 0.0199

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.034
DANN	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7518457; hg19: chr1-202915536;