Genetic Variant ADIPOQ:c.214+135A>G (chr3-186853407-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004797.4(ADIPOQ):c.214+135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 1,168,384 control chromosomes in the GnomAD database, including 9,516 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 1108 hom., cov: 33)

Exomes 𝑓: 0.12 ( 8408 hom. )

Consequence

ADIPOQ
NM_004797.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.627

Publications

55 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ADIPOQ	NM_004797.4 link	c.214+135A>G	intron_variant	Intron 2 of 2	ENST00000320741.7	NP_004788.1
ADIPOQ	NM_001177800.2 link	c.214+135A>G	intron_variant	Intron 3 of 3		NP_001171271.1
ADIPOQ-AS1	NR_046662.2 link	n.2216-165T>C	intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ADIPOQ	ENST00000320741.7 link	c.214+135A>G	intron_variant	Intron 2 of 2	1	NM_004797.4	ENSP00000320709.2
ADIPOQ	ENST00000444204.2 link	c.214+135A>G	intron_variant	Intron 3 of 3	1		ENSP00000389814.2
ADIPOQ-AS1	ENST00000422718.1 link	n.2087-165T>C	intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15941

AN:

152218

Hom.:

1110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0469

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.203

Gnomad EAS

AF:

0.291

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.0434

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.159

GnomAD4 exome

AF:

0.118

AC:

120397

AN:

1016048

Hom.:

8408

AF XY:

0.119

AC XY:

61309

AN XY:

513630

show subpopulations

African (AFR)

AF:

0.0426

AC:

1021

AN:

23962

American (AMR)

AF:

0.180

AC:

6070

AN:

33750

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

4276

AN:

21656

East Asian (EAS)

AF:

0.292

AC:

9876

AN:

33828

South Asian (SAS)

AF:

0.127

AC:

8680

AN:

68352

European-Finnish (FIN)

AF:

0.0446

AC:

2145

AN:

48098

Middle Eastern (MID)

AF:

0.209

AC:

686

AN:

3276

European-Non Finnish (NFE)

AF:

0.111

AC:

81559

AN:

738064

Other (OTH)

AF:

0.135

AC:

6084

AN:

45062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

5178

10357

15535

20714

25892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2686

5372

8058

10744

13430

<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:

0.105

AC:

15944

AN:

152336

Hom.:

1108

Cov.:

AF XY:

0.107

AC XY:

7955

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0469

AC:

1951

AN:

41586

American (AMR)

AF:

0.182

AC:

2789

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.203

AC:

703

AN:

3468

East Asian (EAS)

AF:

0.291

AC:

1507

AN:

5184

South Asian (SAS)

AF:

0.132

AC:

639

AN:

4832

European-Finnish (FIN)

AF:

0.0434

AC:

461

AN:

10626

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.109

AC:

7417

AN:

68016

Other (OTH)

AF:

0.160

AC:

338

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

739

1479

2218

2958

3697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.112

Hom.:

1529

Bravo

AF:

0.113

Asia WGS

AF:

0.208

AC:

720

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.9

(source)

DANN

Benign

0.71

PhyloP100

0.63

Mutation Taster

=100/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over