Genetic Variant ADIPOQ:c.-8-649T>G (chr3-186852402-T-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.-8-649T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0572 in 153,140 control chromosomes in the GnomAD database, including 260 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 0.057 ( 258 hom., cov: 32)

Exomes 𝑓: 0.052 ( 2 hom. )

Consequence

ADIPOQ
NM_004797.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.219

Publications

11 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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ADIPOQ	NM_004797.4 link	c.-8-649T>G	intron_variant	Intron 1 of 2	ENST00000320741.7	NP_004788.1	Q15848A8K660
ADIPOQ-AS1	NR_046662.2 link	n.3056A>C	non_coding_transcript_exon_variant	Exon 4 of 4
ADIPOQ	NM_001177800.2 link	c.-8-649T>G	intron_variant	Intron 2 of 3		NP_001171271.1	Q15848A8K660B2R773

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADIPOQ	ENST00000320741.7 link	c.-8-649T>G	intron_variant	Intron 1 of 2	1	NM_004797.4	ENSP00000320709.2	Q15848
ADIPOQ	ENST00000444204.2 link	c.-8-649T>G	intron_variant	Intron 2 of 3	1		ENSP00000389814.2	Q15848
ADIPOQ-AS1	ENST00000422718.1 link	n.2927A>C	non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.0573

AC:

8711

AN:

152032

Hom.:

258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0600

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.0424

Gnomad ASJ

AF:

0.0899

Gnomad EAS

AF:

0.0254

Gnomad SAS

AF:

0.0394

Gnomad FIN

AF:

0.0433

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0635

Gnomad OTH

AF:

0.0554

GnomAD4 exome

AF:

0.0516

AC:

AN:

988

Hom.:

Cov.:

AF XY:

0.0520

AC XY:

AN XY:

596

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

0.0234

AC:

AN:

128

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

AN:

East Asian (EAS)

AF:

0.0714

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0550

AC:

AN:

746

Other (OTH)

AF:

0.0833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0573

AC:

8711

AN:

152152

Hom.:

258

Cov.:

AF XY:

0.0538

AC XY:

3998

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0599

AC:

2486

AN:

41500

American (AMR)

AF:

0.0423

AC:

645

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0899

AC:

312

AN:

3470

East Asian (EAS)

AF:

0.0255

AC:

132

AN:

5178

South Asian (SAS)

AF:

0.0392

AC:

189

AN:

4816

European-Finnish (FIN)

AF:

0.0433

AC:

459

AN:

10610

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0635

AC:

4318

AN:

67992

Other (OTH)

AF:

0.0548

AC:

116

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

422

844

1265

1687

2109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0613

Hom.:

577

Bravo

AF:

0.0584

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.2

(source)

DANN

Benign

0.64

PhyloP100

0.22

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