chr1-202946408-A-G

Variant names:

• chr1-202946408-A-G
• rs7518457
• NM_015999.6:c.430+31T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0542 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.430+31T>C		intron	N/A	NP_057083.2
	ADIPOR1	NM_001290553.2		c.430+31T>C		intron	N/A	NP_001277482.1
	ADIPOR1	NM_001290557.1		c.430+31T>C		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.430+31T>C		intron	N/A	ENSP00000341785.5
	ADIPOR1	ENST00000367254.7	TSL:1	c.430+31T>C		intron	N/A	ENSP00000356223.3
	ADIPOR1	ENST00000417068.5	TSL:3	c.430+31T>C		intron	N/A	ENSP00000402178.1

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

GnomAD2 exomes AF: 0.00483 AC: 1206 AN: 249938 AF XY: 0.00364

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 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

African (AFR) AF: 0.0622 AC: 2080 AN: 33456

American (AMR) AF: 0.00443 AC: 198 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0103 AC: 269 AN: 26120

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00397 AC: 21 AN: 5296

European-Non Finnish (NFE) AF: 0.000116 AC: 129 AN: 1111630

Other (OTH) AF: 0.00471 AC: 284 AN: 60330

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

African (AFR) AF: 0.0561 AC: 2330 AN: 41510

American (AMR) AF: 0.00831 AC: 127 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68018

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.00826 Hom.: 11

Bravo AF: 0.0199

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.034
DANN	Benign	0.30
PhyloP100		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7518457; hg19: chr1-202915536;