rs17366653

Positions:

• chr3-186853027-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93

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-AS1 (HGNC:40648): (ADIPOQ antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 1296 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADIPOQ	NM_004797.4	c.-8-24T>C		intron_variant		ENST00000320741.7	NP_004788.1
ADIPOQ-AS1	NR_046662.2	n.2431A>G		non_coding_transcript_exon_variant	4/4
ADIPOQ	NM_001177800.2	c.-8-24T>C		intron_variant			NP_001171271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADIPOQ	ENST00000320741.7	c.-8-24T>C		intron_variant		1	NM_004797.4	ENSP00000320709	P1
ADIPOQ	ENST00000444204.2	c.-8-24T>C		intron_variant		1		ENSP00000389814	P1
ADIPOQ-AS1	ENST00000422718.1	n.2302A>G		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.00853 AC: 1298 AN: 152224 Hom.: 14 Cov.: 33

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

GnomAD3 exomes AF: 0.00940 AC: 2345 AN: 249372 Hom.: 25 AF XY: 0.00981 AC XY: 1324 AN XY: 134904

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 SAS exome AF: 0.00382

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.: 30 AF XY: 0.0103 AC XY: 7509 AN XY: 726882

Gnomad4 AFR exome AF: 0.00140

Gnomad4 AMR exome AF: 0.00707

Gnomad4 ASJ exome AF: 0.0242

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00478

Gnomad4 FIN exome AF: 0.00511

Gnomad4 NFE exome AF: 0.0116

Gnomad4 OTH exome AF: 0.00987

GnomAD4 genome AF: 0.00851 AC: 1296 AN: 152342 Hom.: 14 Cov.: 33 AF XY: 0.00804 AC XY: 599 AN XY: 74494

Gnomad4 AFR AF: 0.00164

Gnomad4 AMR AF: 0.00667

Gnomad4 ASJ AF: 0.0207

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.0131

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0127 Hom.: 5

Bravo AF: 0.00884

Asia WGS AF: 0.00144 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.0
DANN	Benign	0.77
BranchPoint Hunter		6.0

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

LitVar

Other links and lift over

dbSNP: rs17366653; hg19: chr3-186570816;