rs822388

Positions:

• chr3-186844495-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004797.4(ADIPOQ):​c.-9+1746A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 142,518 control chromosomes in the GnomAD database, including 11,908 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 0.40 (11908 hom., cov: 23)
• Consequence: ADIPOQ NM_004797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADIPOQ	NM_004797.4	c.-9+1746A>G		intron_variant		ENST00000320741.7	NP_004788.1
ADIPOQ	NM_001177800.2	c.-59-1062A>G		intron_variant			NP_001171271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADIPOQ	ENST00000320741.7	c.-9+1746A>G		intron_variant		1	NM_004797.4	ENSP00000320709.2
ADIPOQ	ENST00000444204.2	c.-59-1062A>G		intron_variant		1		ENSP00000389814.2

Frequencies

GnomAD3 genomes AF: 0.396 AC: 56455 AN: 142424 Hom.: 11893 Cov.: 23

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.396 AC: 56505 AN: 142518 Hom.: 11908 Cov.: 23 AF XY: 0.403 AC XY: 27709 AN XY: 68824

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.368

Alfa AF: 0.332 Hom.: 738

Asia WGS AF: 0.412 AC: 1435 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs822388; hg19: chr3-186562284;