chr1-202945228-T-C

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_015999.6(ADIPOR1):c.431-59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.543 (AC=769,944) in the gnomAD database across 1,418,200 control chromosomes, including 210,210 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.602. 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: 𝑓 0.53 (21299 hom., cov: 32)
  • Exomes 𝑓: 0.54 (188911 hom.)
• Consequence: ADIPOR1 NM_015999.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 71 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: Benign. The variant received -12 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	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).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.6022 — exceeds 5%% threshold (BA1 applied)

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>G	intron	Intron 4 of 7	Prot: NP_057083.2
	ADIPOR1 NM_001290553.2		c.431-59A>G	intron	Intron 4 of 7	Prot: NP_001277482.1 UniProt:
	ADIPOR1 NM_001290557.1		c.431-59A>G	intron	Intron 5 of 8	Prot: NP_001277486.1 UniProt:

ADIPOR1 NM_015999.6

MANE Select

HGVSc / HGVSpc.431-59A>G

Exon rankIntron 4 of 7

intron

Prot: NP_057083.2

ADIPOR1 NM_001290553.2

HGVSc / HGVSpc.431-59A>G

Exon rankIntron 4 of 7

intron

Prot: NP_001277482.1UniProt: Q96A54

ADIPOR1 NM_001290557.1

HGVSc / HGVSpc.431-59A>G

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>G	intron	Intron 4 of 7	Prot: ENSP00000341785.5 UniProt:
	ADIPOR1 ENST00000367254.7	TSL:1	c.430+1211A>G	intron	Intron 4 of 6	Prot: ENSP00000356223.3 UniProt:
	ADIPOR1 ENST00000855702.1		c.431-59A>G	intron	Intron 4 of 7	Prot: ENSP00000525761.1 UniProt:

ADIPOR1 ENST00000340990.10

TSL:1MANE Select

HGVSc / HGVSpc.431-59A>G

Exon rankIntron 4 of 7

intron

Prot: ENSP00000341785.5UniProt: Q96A54

ADIPOR1 ENST00000367254.7

TSL:1

HGVSc / HGVSpc.430+1211A>G

Exon rankIntron 4 of 6

intron

Prot: ENSP00000356223.3UniProt: F8W782

ADIPOR1 ENST00000855702.1

HGVSc / HGVSpc.431-59A>G

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 5 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.528	AC:80196	Hom:21263	AN:151976	Cov:32
GnomAD4 exome	AF: 0.545	AC:689667	Hom:188911	AN:1266106	Cov:
GnomAD4 genome	AF: 0.528	AC:80277	Hom:21299	AN:152094	Cov:32
TOPMed (Bravo)	AF: 0.526	AC:139325	Hom:36882	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.536	AC:145530	Hom:39098	AN:271324	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.529	AC:1240	Hom:327	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.636	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.517	AC:155	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.578	AC:2008	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.552	AC:3995	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.386	AC:68	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.514	AC:63052	Hom:16282	AN:122706	Cov:
Turkish Variome	AF: 0.462	AC:715	Hom:160	AN:1546	Cov:
UK10K	AF: 0.560	AC:4233	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.646	AC:5785	Hom:1883	AN:8960	Cov:

Showing 15 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.403	22130	54924	0.390	35817	91882

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.87
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.52
DANN	Benign	0.66
GPN-Star LLR	N/A	2.6
GPN-Star score	N/A	-1.3
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-1.7

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	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