chr1-202948219-G-T

Variant names:

• chr1-202948219-G-T
• rs34010966
• NM_015999.6:c.258+85C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015999.6(ADIPOR1):​c.258+85C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000316 in 950,030 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: ADIPOR1 NM_015999.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOR1	NM_015999.6	c.258+85C>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+85C>A		intron_variant	Intron 3 of 7	1	NM_015999.6	ENSP00000341785.5
ADIPOR1	ENST00000367254.7	c.258+85C>A		intron_variant	Intron 3 of 6	1		ENSP00000356223.3
ADIPOR1	ENST00000417068.5	c.258+85C>A		intron_variant	Intron 4 of 6	3		ENSP00000402178.1
ADIPOR1	ENST00000426229.1	c.258+85C>A		intron_variant	Intron 4 of 5	2		ENSP00000392946.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000316 AC: 3 AN: 950030 Hom.: 0 AF XY: 0.00000418 AC XY: 2 AN XY: 478648

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20750

American (AMR) AF: 0.00 AC: 0 AN: 24832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16554

East Asian (EAS) AF: 0.00 AC: 0 AN: 33478

South Asian (SAS) AF: 0.00 AC: 0 AN: 58236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2874

European-Non Finnish (NFE) AF: 0.00000426 AC: 3 AN: 704304

Other (OTH) AF: 0.00 AC: 0 AN: 41916

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.11
DANN	Benign	0.43
PhyloP100		-0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs34010966; hg19: chr1-202917347;