1-202947678-C-T

Variant names:

• chr1-202947678-C-T
• rs12045862
• NM_015999.6:c.258+626G>A

Variant summary

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

The NM_015999.6(ADIPOR1):​c.258+626G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,060 control chromosomes in the GnomAD database, including 5,694 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 0.25 (5694 hom., cov: 32)
• Consequence: ADIPOR1 NM_015999.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 21 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOR1	NM_015999.6	c.258+626G>A		intron_variant	Intron 3 of 7	ENST00000340990.10	NP_057083.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADIPOR1	ENST00000340990.10	c.258+626G>A		intron_variant	Intron 3 of 7	1	NM_015999.6	ENSP00000341785.5
ADIPOR1	ENST00000367254.7	c.258+626G>A		intron_variant	Intron 3 of 6	1		ENSP00000356223.3
ADIPOR1	ENST00000417068.5	c.258+626G>A		intron_variant	Intron 4 of 6	3		ENSP00000402178.1
ADIPOR1	ENST00000426229.1	c.258+626G>A		intron_variant	Intron 4 of 5	2		ENSP00000392946.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37677 AN: 151942 Hom.: 5680 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.238

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.248 AC: 37725 AN: 152060 Hom.: 5694 Cov.: 32 AF XY: 0.257 AC XY: 19089 AN XY: 74310

African (AFR) AF: 0.110 AC: 4567 AN: 41508

American (AMR) AF: 0.369 AC: 5632 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 947 AN: 3468

East Asian (EAS) AF: 0.572 AC: 2954 AN: 5164

South Asian (SAS) AF: 0.410 AC: 1973 AN: 4818

European-Finnish (FIN) AF: 0.289 AC: 3045 AN: 10538

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17888 AN: 67970

Other (OTH) AF: 0.239 AC: 505 AN: 2116

Alfa AF: 0.247 Hom.: 5845

Bravo AF: 0.246

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.55
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs12045862; hg19: chr1-202916806;