Genetic Variant NM_015999.6:c.430+12G>A (chr1-202946427-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015999.6(ADIPOR1):c.430+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0441 in 1,613,514 control chromosomes in the GnomAD database, including 2,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 175 hom., cov: 31)

Exomes 𝑓: 0.044 ( 1879 hom. )

Consequence

ADIPOR1
NM_015999.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.295

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-202946427-C-T is Benign according to our data. Variant chr1-202946427-C-T is described in ClinVar as [Benign]. Clinvar id is 1168437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOR1	NM_015999.6 link	c.430+12G>A		intron_variant	Intron 4 of 7	ENST00000340990.10	NP_057083.2	Q96A54

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADIPOR1	ENST00000340990.10 link	c.430+12G>A	intron_variant	Intron 4 of 7	1	NM_015999.6	ENSP00000341785.5	Q96A54
ADIPOR1	ENST00000367254.7 link	c.430+12G>A	intron_variant	Intron 4 of 6	1		ENSP00000356223.3	F8W782
ADIPOR1	ENST00000417068.5 link	c.430+12G>A	intron_variant	Intron 5 of 6	3		ENSP00000402178.1	C9JNM5
ADIPOR1	ENST00000426229.1 link	c.430+12G>A	intron_variant	Intron 5 of 5	2		ENSP00000392946.1	C9J0W7

Frequencies

GnomAD3 genomes

AF:

0.0416

AC:

6317

AN:

151934

Hom.:

172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0428

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0242

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0292

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.0371

Gnomad OTH

AF:

0.0421

GnomAD3 exomes

AF:

0.0478

AC:

11987

AN:

250726

Hom.:

401

AF XY:

0.0511

AC XY:

6922

AN XY:

135504

show subpopulations

Gnomad AFR exome

AF:

0.0416

Gnomad AMR exome

AF:

0.0185

Gnomad ASJ exome

AF:

0.0412

Gnomad EAS exome

AF:

0.0951

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.0320

Gnomad NFE exome

AF:

0.0382

Gnomad OTH exome

AF:

0.0440

GnomAD4 exome

AF:

0.0443

AC:

64798

AN:

1461462

Hom.:

1879

Cov.:

AF XY:

0.0464

AC XY:

33733

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.0445

Gnomad4 AMR exome

AF:

0.0193

Gnomad4 ASJ exome

AF:

0.0411

Gnomad4 EAS exome

AF:

0.114

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.0334

Gnomad4 NFE exome

AF:

0.0389

Gnomad4 OTH exome

AF:

0.0477

GnomAD4 genome

AF:

0.0416

AC:

6331

AN:

152052

Hom.:

175

Cov.:

AF XY:

0.0420

AC XY:

3119

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0431

Gnomad4 AMR

AF:

0.0242

Gnomad4 ASJ

AF:

0.0375

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.0292

Gnomad4 NFE

AF:

0.0371

Gnomad4 OTH

AF:

0.0417

Alfa

AF:

0.0393

Hom.:

190

Bravo

AF:

0.0394

Asia WGS

AF:

0.110

AC:

385

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.5

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over