rs822388

Variant names:

• chr3-186844495-A-G
• rs822388
• NM_004797.4:c.-9+1746A>G

Variant summary

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

The ENST00000320741.7(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 ENST00000320741.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799
• Publications: 1 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000320741.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOQ	NM_004797.4	MANE Select	c.-9+1746A>G		intron	N/A	NP_004788.1
	ADIPOQ	NM_001177800.2		c.-59-1062A>G		intron	N/A	NP_001171271.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOQ	ENST00000320741.7	TSL:1 MANE Select	c.-9+1746A>G		intron	N/A	ENSP00000320709.2
	ADIPOQ	ENST00000444204.2	TSL:1	c.-59-1062A>G		intron	N/A	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

African (AFR) AF: 0.535 AC: 20147 AN: 37630

American (AMR) AF: 0.429 AC: 5971 AN: 13906

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1167 AN: 3372

East Asian (EAS) AF: 0.482 AC: 2327 AN: 4824

South Asian (SAS) AF: 0.278 AC: 1216 AN: 4370

European-Finnish (FIN) AF: 0.479 AC: 4361 AN: 9106

Middle Eastern (MID) AF: 0.319 AC: 88 AN: 276

European-Non Finnish (NFE) AF: 0.304 AC: 20157 AN: 66214

Other (OTH) AF: 0.368 AC: 713 AN: 1938

Alfa AF: 0.332 Hom.: 738

Asia WGS AF: 0.412 AC: 1435 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.64
PhyloP100		-0.80
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: rs822388; hg19: chr3-186562284;