rs2275737

Positions:

• chr1-202951172-A-C
• chr1-202951172-A-T

Variant summary

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

The NM_015999.6(ADIPOR1):​c.-94-8T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,366,868 control chromosomes in the GnomAD database, including 231,512 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.58 (25296 hom., cov: 31)
  • Exomes 𝑓: 0.58 (206216 hom.)
• Consequence: ADIPOR1 NM_015999.6 splice_region, intron
• Scores: Splicing: ADA: 0.001928
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

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=-0.6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADIPOR1	NM_015999.6	c.-94-8T>G		splice_region_variant, intron_variant		ENST00000340990.10	NP_057083.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADIPOR1	ENST00000340990.10	c.-94-8T>G		splice_region_variant, intron_variant		1	NM_015999.6	ENSP00000341785.5
ADIPOR1	ENST00000367254.7	c.-94-8T>G		splice_region_variant, intron_variant		1		ENSP00000356223.3
ADIPOR1	ENST00000417068.5	c.-94-8T>G		splice_region_variant, intron_variant		3		ENSP00000402178.1
ADIPOR1	ENST00000426229.1	c.-94-8T>G		splice_region_variant, intron_variant		2		ENSP00000392946.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87123 AN: 151340 Hom.: 25246 Cov.: 31

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.570

GnomAD4 exome AF: 0.579 AC: 703327 AN: 1215410 Hom.: 206216 Cov.: 16 AF XY: 0.577 AC XY: 350176 AN XY: 607032

Gnomad4 AFR exome AF: 0.570

Gnomad4 AMR exome AF: 0.647

Gnomad4 ASJ exome AF: 0.467

Gnomad4 EAS exome AF: 0.817

Gnomad4 SAS exome AF: 0.549

Gnomad4 FIN exome AF: 0.543

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.572

GnomAD4 genome AF: 0.576 AC: 87232 AN: 151458 Hom.: 25296 Cov.: 31 AF XY: 0.576 AC XY: 42630 AN XY: 73962

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.828

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.575

Alfa AF: 0.574 Hom.: 3665

Bravo AF: 0.583

Asia WGS AF: 0.705 AC: 2451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0019
dbscSNV1_RF	Benign	0.17
SpliceAI score (max)		0.010		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: rs2275737; hg19: chr1-202920300;