chr3-186854300-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004797.4(ADIPOQ):c.331T>C(p.Tyr111His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 1,614,206 control chromosomes in the GnomAD database, including 727 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.020 ( 50 hom., cov: 31)

Exomes 𝑓: 0.028 ( 677 hom. )

Consequence

ADIPOQ
NM_004797.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.271

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059143007).

BP6

Variant 3-186854300-T-C is Benign according to our data. Variant chr3-186854300-T-C is described in ClinVar as [Benign]. Clinvar id is 3042029.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0205 (3118/152328) while in subpopulation NFE AF = 0.0297 (2019/68024). AF 95% confidence interval is 0.0286. There are 50 homozygotes in GnomAd4. There are 1518 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 3118 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOQ	NM_004797.4 link	c.331T>C	p.Tyr111His	missense_variant	Exon 3 of 3	ENST00000320741.7	NP_004788.1	Q15848A8K660
ADIPOQ	NM_001177800.2 link	c.331T>C	p.Tyr111His	missense_variant	Exon 4 of 4		NP_001171271.1	Q15848A8K660B2R773
ADIPOQ-AS1	NR_046662.2 link	n.1953A>G		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.331T>C	p.Tyr111His	missense_variant	Exon 3 of 3	1	NM_004797.4	ENSP00000320709.2	Q15848
ADIPOQ	ENST00000444204.2 link	c.331T>C	p.Tyr111His	missense_variant	Exon 4 of 4	1		ENSP00000389814.2	Q15848
ADIPOQ-AS1	ENST00000422718.1 link	n.1824A>G		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3118

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00605

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0125

Gnomad ASJ

AF:

0.0372

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00932

Gnomad FIN

AF:

0.0387

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0297

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.0219

AC:

5516

AN:

251458

AF XY:

0.0227

show subpopulations

Gnomad AFR exome

AF:

0.00714

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.0339

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0387

Gnomad NFE exome

AF:

0.0291

Gnomad OTH exome

AF:

0.0274

GnomAD4 exome

AF:

0.0285

AC:

41648

AN:

1461878

Hom.:

677

Cov.:

AF XY:

0.0280

AC XY:

20361

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00430

AC:

144

AN:

33480

Gnomad4 AMR exome

AF:

0.0107

AC:

478

AN:

44724

Gnomad4 ASJ exome

AF:

0.0325

AC:

849

AN:

26134

Gnomad4 EAS exome

AF:

0.0000252

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.0127

AC:

1097

AN:

86258

Gnomad4 FIN exome

AF:

0.0369

AC:

1973

AN:

53420

Gnomad4 NFE exome

AF:

0.0319

AC:

35477

AN:

1111998

Gnomad4 Remaining exome

AF:

0.0254

AC:

1533

AN:

60396

Heterozygous variant carriers

2599

5199

7798

10398

12997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

1362

2724

4086

5448

6810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0205

AC:

3118

AN:

152328

Hom.:

Cov.:

AF XY:

0.0204

AC XY:

1518

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00604

AC:

0.00603627

AN:

0.00603627

Gnomad4 AMR

AF:

0.0125

AC:

0.0124788

AN:

0.0124788

Gnomad4 ASJ

AF:

0.0372

AC:

0.0371758

AN:

0.0371758

Gnomad4 EAS

AF:

0.000966

AC:

0.000965624

AN:

0.000965624

Gnomad4 SAS

AF:

0.00974

AC:

0.00973891

AN:

0.00973891

Gnomad4 FIN

AF:

0.0387

AC:

0.0387006

AN:

0.0387006

Gnomad4 NFE

AF:

0.0297

AC:

0.0296807

AN:

0.0296807

Gnomad4 OTH

AF:

0.0147

AC:

0.0146503

AN:

0.0146503

Heterozygous variant carriers

164

328

493

657

821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0263

Hom.:

247

Bravo

AF:

0.0185

TwinsUK

AF:

0.0316

AC:

117

ALSPAC

AF:

0.0350

AC:

135

ESP6500AA

AF:

0.00772

AC:

ESP6500EA

AF:

0.0320

AC:

275

ExAC

AF:

0.0212

AC:

2569

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0278

EpiControl

AF:

0.0285

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ADIPOQ-related disorder

Benign:1

Sep 24, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as 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

Benign

0.12

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.32

T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.78

.;T

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

L;L

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.075

Sift

Benign

0.51

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.0060

B;B

Vest4

0.032

ClinPred

0.020

GERP RS

3.1

Varity_R

0.20

gMVP

0.46

Mutation Taster

=99/1

polymorphism (auto)

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

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