dbSNP rs17366653: ADIPOQ:c.-8-24T>C (chr3-186853027-T-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_004797.4(ADIPOQ):c.-8-24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,402 control chromosomes in the GnomAD database, including 120 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.0085 ( 14 hom., cov: 33)

Exomes 𝑓: 0.010 ( 106 hom. )

Consequence

ADIPOQ
NM_004797.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.93

Publications

17 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: Likely_benign. The variant received -3 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BS2

High Homozygotes in GnomAd4 at 14 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004797.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADIPOQ	NM_004797.4	MANE Select	c.-8-24T>C	intron	N/A	NP_004788.1	Q15848
ADIPOQ	NM_001177800.2		c.-8-24T>C	intron	N/A	NP_001171271.1	A8K660
ADIPOQ-AS1	NR_046662.2		n.2431A>G	non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADIPOQ	ENST00000320741.7	TSL:1 MANE Select	c.-8-24T>C	intron	N/A	ENSP00000320709.2	Q15848
ADIPOQ	ENST00000444204.2	TSL:1	c.-8-24T>C	intron	N/A	ENSP00000389814.2	Q15848
ADIPOQ	ENST00000956685.1		c.-32T>C	5_prime_UTR	Exon 1 of 2	ENSP00000626744.1

Frequencies

GnomAD3 genomes

AF:

0.00853

AC:

1298

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.00668

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00475

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00940

AC:

2345

AN:

249372

AF XY:

0.00981

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00698

Gnomad ASJ exome

AF:

0.0241

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00412

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.0158

GnomAD4 exome

AF:

0.0104

AC:

15222

AN:

1461060

Hom.:

106

Cov.:

AF XY:

0.0103

AC XY:

7509

AN XY:

726882

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

33468

American (AMR)

AF:

0.00707

AC:

316

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0242

AC:

633

AN:

26122

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00478

AC:

412

AN:

86178

European-Finnish (FIN)

AF:

0.00511

AC:

273

AN:

53414

Middle Eastern (MID)

AF:

0.0142

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0116

AC:

12862

AN:

1111338

Other (OTH)

AF:

0.00987

AC:

596

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

816

1632

2447

3263

4079

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.00851

AC:

1296

AN:

152342

Hom.:

Cov.:

AF XY:

0.00804

AC XY:

599

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

41588

American (AMR)

AF:

0.00667

AC:

102

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0207

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00476

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00358

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0131

AC:

890

AN:

68022

Other (OTH)

AF:

0.0151

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

136

203

271

339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0127

Hom.:

Bravo

AF:

0.00884

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

9.0

(source)

DANN

Benign

0.77

PhyloP100

2.9

BranchPoint Hunter

6.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.59

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.59

Position offset: 24

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over