chr1-202945228-T-G

Variant names:

• chr1-202945228-T-G
• rs1342387
• NM_015999.6:c.431-59A>C

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-3 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -3 classification points (ACMG Germline Pathogenicity v2019). PM2_SupportingBP4_Strong

The NM_015999.6(ADIPOR1):c.431-59A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.000000788 (AC=1) in the gnomAD database across 1,268,372 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.0000168. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) 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: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: ADIPOR1 NM_015999.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 6 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: SD, AD Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Franklin by Genoox

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -3 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Rare in gnomAD for AD/XL gene (popmax AF below threshold) — PM2 Supporting; GnomAD popmax AF = 0.0000168 — borderline rare for AD/XL gene (threshold 0.0001) — PM2 supporting.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ADIPOR1 NM_015999.6	MANE Select	c.431-59A>C	intron	Intron 4 of 7	Prot: NP_057083.2
	ADIPOR1 NM_001290553.2		c.431-59A>C	intron	Intron 4 of 7	Prot: NP_001277482.1 UniProt:
	ADIPOR1 NM_001290557.1		c.431-59A>C	intron	Intron 5 of 8	Prot: NP_001277486.1 UniProt:

ADIPOR1 NM_015999.6

MANE Select

HGVSc / HGVSpc.431-59A>C

Exon rankIntron 4 of 7

intron

Prot: NP_057083.2

ADIPOR1 NM_001290553.2

HGVSc / HGVSpc.431-59A>C

Exon rankIntron 4 of 7

intron

Prot: NP_001277482.1UniProt: Q96A54

ADIPOR1 NM_001290557.1

HGVSc / HGVSpc.431-59A>C

Exon rankIntron 5 of 8

intron

Prot: NP_001277486.1UniProt: Q96A54

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ADIPOR1 ENST00000340990.10	TSL:1MANE Select	c.431-59A>C	intron	Intron 4 of 7	Prot: ENSP00000341785.5 UniProt:
	ADIPOR1 ENST00000367254.7	TSL:1	c.430+1211A>C	intron	Intron 4 of 6	Prot: ENSP00000356223.3 UniProt:
	ADIPOR1 ENST00000855702.1		c.431-59A>C	intron	Intron 4 of 7	Prot: ENSP00000525761.1 UniProt:

ADIPOR1 ENST00000340990.10

TSL:1MANE Select

HGVSc / HGVSpc.431-59A>C

Exon rankIntron 4 of 7

intron

Prot: ENSP00000341785.5UniProt: Q96A54

ADIPOR1 ENST00000367254.7

TSL:1

HGVSc / HGVSpc.430+1211A>C

Exon rankIntron 4 of 6

intron

Prot: ENSP00000356223.3UniProt: F8W782

ADIPOR1 ENST00000855702.1

HGVSc / HGVSpc.431-59A>C

Exon rankIntron 4 of 7

intron

Prot: ENSP00000525761.1UniProt: Q96A54

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 exome	AF: 7.88e-7	AC:1	Hom:0	AN:1268372	Cov:
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	1.5
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.56
DANN	Benign	0.67
GPN-Star LLR	N/A	0.24
GPN-Star score	N/A	-0.24
PhyloP100	Benign	-1.7

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.010
SpliceAI score (max)	Benign	0.020	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs1342387;

hg19: chr1-202914356;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar