3-186854237-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP4_StrongBP6_Very_StrongBS2

The NM_004797.4(ADIPOQ):c.268G>A(p.Gly90Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00317 in 1,613,664 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0032 ( 15 hom. )

Consequence

ADIPOQ
NM_004797.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 9.94

Publications

47 publications found

Variant links:

Genes affected

ADIPOQ (HGNC:13633): (adiponectin, C1Q and collagen domain containing) This gene is expressed in adipose tissue exclusively. It encodes a protein with similarity to collagens X and VIII and complement factor C1q. The encoded protein circulates in the plasma and is involved with metabolic and hormonal processes. Mutations in this gene are associated with adiponectin deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Apr 2010]

ADIPOQ links:

ADIPOQ-AS1 (HGNC:40648): (ADIPOQ antisense RNA 1)

ADIPOQ-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 11: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, Eigen, M_CAP, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.025646985).

BP6

Variant 3-186854237-G-A is Benign according to our data. Variant chr3-186854237-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 789279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOQ	NM_004797.4 link	c.268G>A	p.Gly90Ser	missense_variant	Exon 3 of 3	ENST00000320741.7	NP_004788.1	Q15848A8K660
ADIPOQ	NM_001177800.2 link	c.268G>A	p.Gly90Ser	missense_variant	Exon 4 of 4		NP_001171271.1	Q15848A8K660B2R773
ADIPOQ-AS1	NR_046662.2 link	n.2016C>T		non_coding_transcript_exon_variant	Exon 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADIPOQ	ENST00000320741.7 link	c.268G>A	p.Gly90Ser	missense_variant	Exon 3 of 3	1	NM_004797.4	ENSP00000320709.2	Q15848
ADIPOQ	ENST00000444204.2 link	c.268G>A	p.Gly90Ser	missense_variant	Exon 4 of 4	1		ENSP00000389814.2	Q15848
ADIPOQ-AS1	ENST00000422718.1 link	n.1887C>T		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.00283

AC:

431

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00478

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00299

AC:

752

AN:

251152

AF XY:

0.00309

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.00609

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000694

Gnomad NFE exome

AF:

0.00482

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00320

AC:

4679

AN:

1461326

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

2338

AN XY:

726886

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

33458

American (AMR)

AF:

0.00224

AC:

100

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.00567

AC:

148

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.000835

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.000674

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.0111

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00358

AC:

3980

AN:

1111596

Other (OTH)

AF:

0.00394

AC:

238

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

275

551

826

1102

1377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00283

AC:

431

AN:

152338

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41578

American (AMR)

AF:

0.00189

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00478

AC:

325

AN:

68028

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00409

Hom.:

Bravo

AF:

0.00301

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00581

AC:

ExAC

AF:

0.00302

AC:

367

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00589

EpiControl

AF:

0.00616

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ADIPOQ-related disorder

Benign:1

Jan 21, 2022

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.60

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.97

D;D

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

.;D

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.026

T;T

MetaSVM

Pathogenic

0.82

MutationAssessor

Pathogenic

3.4

M;M

PhyloP100

9.9

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Pathogenic

0.97

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.72

MVP

0.94

ClinPred

0.067

GERP RS

5.5

Varity_R

0.97

gMVP

0.85

Mutation Taster

=98/2

polymorphism

(source)

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

Publications

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3-186854237-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over