chr1-202951176-T-C

Variant names:

• chr1-202951176-T-C
• rs2275738
• NM_015999.6:c.-94-12A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015999.6(ADIPOR1):​c.-94-12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 1,322,382 control chromosomes in the GnomAD database, including 224,413 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 0.58 (25789 hom., cov: 31)
  • Exomes 𝑓: 0.58 (198624 hom.)
• Consequence: ADIPOR1 NM_015999.6 intron
• Scores: Splicing: ADA: 0.0001699
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• Publications: 10 publications found

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]

ADIPOR1 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AD Classification: LIMITED Submitted by: Franklin by Genoox

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOR1	NM_015999.6	c.-94-12A>G		intron_variant	Intron 1 of 7	ENST00000340990.10	NP_057083.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADIPOR1	ENST00000340990.10	c.-94-12A>G		intron_variant	Intron 1 of 7	1	NM_015999.6	ENSP00000341785.5
ADIPOR1	ENST00000367254.7	c.-94-12A>G		intron_variant	Intron 1 of 6	1		ENSP00000356223.3
ADIPOR1	ENST00000417068.5	c.-94-12A>G		intron_variant	Intron 2 of 6	3		ENSP00000402178.1
ADIPOR1	ENST00000426229.1	c.-94-12A>G		intron_variant	Intron 2 of 5	2		ENSP00000392946.1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 87952 AN: 151308 Hom.: 25740 Cov.: 31

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.577

GnomAD4 exome AF: 0.579 AC: 677523 AN: 1170956 Hom.: 198624 Cov.: 15 AF XY: 0.577 AC XY: 337986 AN XY: 585872

African (AFR) AF: 0.589 AC: 15652 AN: 26570

American (AMR) AF: 0.646 AC: 19796 AN: 30626

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 9378 AN: 20104

East Asian (EAS) AF: 0.817 AC: 30876 AN: 37780

South Asian (SAS) AF: 0.549 AC: 38292 AN: 69808

European-Finnish (FIN) AF: 0.544 AC: 26218 AN: 48200

Middle Eastern (MID) AF: 0.448 AC: 1855 AN: 4142

European-Non Finnish (NFE) AF: 0.574 AC: 506859 AN: 883788

Other (OTH) AF: 0.573 AC: 28597 AN: 49938

GnomAD4 genome AF: 0.582 AC: 88062 AN: 151426 Hom.: 25789 Cov.: 31 AF XY: 0.582 AC XY: 43023 AN XY: 73956

African (AFR) AF: 0.593 AC: 24447 AN: 41234

American (AMR) AF: 0.614 AC: 9351 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1638 AN: 3468

East Asian (EAS) AF: 0.828 AC: 4260 AN: 5144

South Asian (SAS) AF: 0.575 AC: 2768 AN: 4812

European-Finnish (FIN) AF: 0.523 AC: 5469 AN: 10460

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.568 AC: 38485 AN: 67774

Other (OTH) AF: 0.581 AC: 1221 AN: 2100

Alfa AF: 0.580 Hom.: 3183

Bravo AF: 0.590

Asia WGS AF: 0.706 AC: 2453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.85
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00017
dbscSNV1_RF	Benign	0.050
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: rs2275738; hg19: chr1-202920304;