rs182052

Variant names:

• chr3-186842993-G-A
• rs182052
• NM_004797.4:c.-9+244G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004797.4(ADIPOQ):​c.-9+244G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,082 control chromosomes in the GnomAD database, including 11,284 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 0.38 (11284 hom., cov: 32)
• Consequence: ADIPOQ NM_004797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246
• Publications: 152 publications found

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 Gene-Disease associations (from GenCC):

• STAT3-related early-onset multisystem autoimmune disease

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOQ	NM_004797.4	c.-9+244G>A		intron_variant	Intron 1 of 2	ENST00000320741.7	NP_004788.1
ADIPOQ	NM_001177800.2	c.-60+244G>A		intron_variant	Intron 1 of 3		NP_001171271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADIPOQ	ENST00000320741.7	c.-9+244G>A		intron_variant	Intron 1 of 2	1	NM_004797.4	ENSP00000320709.2
ADIPOQ	ENST00000444204.2	c.-60+244G>A		intron_variant	Intron 1 of 3	1		ENSP00000389814.2

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57164 AN: 151964 Hom.: 11272 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.342

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.376 AC: 57220 AN: 152082 Hom.: 11284 Cov.: 32 AF XY: 0.386 AC XY: 28716 AN XY: 74314

African (AFR) AF: 0.365 AC: 15145 AN: 41472

American (AMR) AF: 0.414 AC: 6327 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1212 AN: 3470

East Asian (EAS) AF: 0.443 AC: 2287 AN: 5162

South Asian (SAS) AF: 0.340 AC: 1641 AN: 4820

European-Finnish (FIN) AF: 0.575 AC: 6076 AN: 10576

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23194 AN: 67986

Other (OTH) AF: 0.343 AC: 721 AN: 2104

Alfa AF: 0.349 Hom.: 29140

Bravo AF: 0.366

Asia WGS AF: 0.416 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.49
PhyloP100		-0.25
PromoterAI		-0.0036	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs182052; hg19: chr3-186560782;