rs17366743

Positions:

chr3-186854300-T-C

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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 same amino acid change has been previously reported as Likely benignin 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 made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3118 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADIPOQ	NM_004797.4 linkuse as main transcript	c.331T>C	p.Tyr111His	missense_variant	3/3	ENST00000320741.7	NP_004788.1
ADIPOQ-AS1	NR_046662.2 linkuse as main transcript	n.1953A>G		non_coding_transcript_exon_variant	2/4
ADIPOQ	NM_001177800.2 linkuse as main transcript	c.331T>C	p.Tyr111His	missense_variant	4/4		NP_001171271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ADIPOQ	ENST00000320741.7 linkuse as main transcript	c.331T>C	p.Tyr111His	missense_variant	3/3	1	NM_004797.4	ENSP00000320709	P1
ADIPOQ	ENST00000444204.2 linkuse as main transcript	c.331T>C	p.Tyr111His	missense_variant	4/4	1		ENSP00000389814	P1
ADIPOQ-AS1	ENST00000422718.1 linkuse as main transcript	n.1824A>G		non_coding_transcript_exon_variant	1/3	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

GnomAD3 exomes

AF:

0.0219

AC:

5516

AN:

251458

Hom.:

AF XY:

0.0227

AC XY:

3086

AN XY:

135896

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 SAS exome

AF:

0.0126

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

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.0325

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0127

Gnomad4 FIN exome

AF:

0.0369

Gnomad4 NFE exome

AF:

0.0319

Gnomad4 OTH exome

AF:

0.0254

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

Gnomad4 AMR

AF:

0.0125

Gnomad4 ASJ

AF:

0.0372

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.00974

Gnomad4 FIN

AF:

0.0387

Gnomad4 NFE

AF:

0.0297

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0278

Hom.:

135

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 2019

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

MutationTaster

Benign

1.0

N;N;N

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

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