1-202951172-A-T

Variant names:

• chr1-202951172-A-T
• rs2275737
• NM_015999.6:c.-94-8T>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.-94-8T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADIPOR1 NM_015999.6 splice_region, intron
• Scores: Splicing: ADA: 0.005033
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 19 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=-0.5).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOR1	NM_015999.6	c.-94-8T>A		splice_region_variant, 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.-94-8T>A		splice_region_variant, intron_variant	Intron 1 of 7	1	NM_015999.6	ENSP00000341785.5
ADIPOR1	ENST00000367254.7	c.-94-8T>A		splice_region_variant, intron_variant	Intron 1 of 6	1		ENSP00000356223.3
ADIPOR1	ENST00000417068.5	c.-94-8T>A		splice_region_variant, intron_variant	Intron 2 of 6	3		ENSP00000402178.1
ADIPOR1	ENST00000426229.1	c.-94-8T>A		splice_region_variant, intron_variant	Intron 2 of 5	2		ENSP00000392946.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1217944 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 608240

African (AFR) AF: 0.00 AC: 0 AN: 27426

American (AMR) AF: 0.00 AC: 0 AN: 31924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20764

East Asian (EAS) AF: 0.00 AC: 0 AN: 38078

South Asian (SAS) AF: 0.00 AC: 0 AN: 72034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4358

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 922786

Other (OTH) AF: 0.00 AC: 0 AN: 51424

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	10
DANN	Benign	0.65
PhyloP100		-0.087

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0050
dbscSNV1_RF	Benign	0.17
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: rs2275737; hg19: chr1-202920300;