1-202945425-C-T

Variant names:

• chr1-202945425-C-T
• rs1342386
• NM_015999.6:c.431-256G>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.431-256G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 152,088 control chromosomes in the GnomAD database, including 21,289 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 0.53 (21289 hom., cov: 33)
• Consequence: ADIPOR1 NM_015999.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.667
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015999.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOR1	NM_015999.6	MANE Select	c.431-256G>A		intron	N/A	NP_057083.2
	ADIPOR1	NM_001290553.2		c.431-256G>A		intron	N/A	NP_001277482.1
	ADIPOR1	NM_001290557.1		c.431-256G>A		intron	N/A	NP_001277486.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOR1	ENST00000340990.10	TSL:1 MANE Select	c.431-256G>A		intron	N/A	ENSP00000341785.5
	ADIPOR1	ENST00000367254.7	TSL:1	c.430+1014G>A		intron	N/A	ENSP00000356223.3
	ADIPOR1	ENST00000417068.5	TSL:3	c.431-256G>A		intron	N/A	ENSP00000402178.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80181 AN: 151974 Hom.: 21253 Cov.: 33

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.528 AC: 80261 AN: 152088 Hom.: 21289 Cov.: 33 AF XY: 0.525 AC XY: 39050 AN XY: 74336

African (AFR) AF: 0.521 AC: 21632 AN: 41484

American (AMR) AF: 0.483 AC: 7382 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1635 AN: 3470

East Asian (EAS) AF: 0.621 AC: 3211 AN: 5170

South Asian (SAS) AF: 0.519 AC: 2501 AN: 4818

European-Finnish (FIN) AF: 0.479 AC: 5071 AN: 10576

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.549 AC: 37286 AN: 67976

Other (OTH) AF: 0.534 AC: 1126 AN: 2110

Alfa AF: 0.533 Hom.: 2575

Bravo AF: 0.526

Asia WGS AF: 0.577 AC: 2005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.31
PhyloP100		-0.67
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: rs1342386; hg19: chr1-202914553;