NM_004797.4:c.-8-4033C>A

Variant names:

• chr3-186849018-C-A
• rs822395
• NM_004797.4:c.-8-4033C>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.-8-4033C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 151,928 control chromosomes in the GnomAD database, including 32,601 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 0.65 (32601 hom., cov: 31)
• Consequence: ADIPOQ NM_004797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 62 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOQ	NM_004797.4	MANE Select	c.-8-4033C>A		intron	N/A	NP_004788.1	Q15848
	ADIPOQ	NM_001177800.2		c.-9+3411C>A		intron	N/A	NP_001171271.1	A8K660

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOQ	ENST00000320741.7	TSL:1 MANE Select	c.-8-4033C>A		intron	N/A	ENSP00000320709.2	Q15848
	ADIPOQ	ENST00000444204.2	TSL:1	c.-9+3411C>A		intron	N/A	ENSP00000389814.2	Q15848
	ADIPOQ	ENST00000881747.1		c.-9+3411C>A		intron	N/A	ENSP00000551806.1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 98932 AN: 151810 Hom.: 32567 Cov.: 31

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.652 AC: 99010 AN: 151928 Hom.: 32601 Cov.: 31 AF XY: 0.655 AC XY: 48649 AN XY: 74238

African (AFR) AF: 0.581 AC: 24052 AN: 41390

American (AMR) AF: 0.707 AC: 10805 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2302 AN: 3470

East Asian (EAS) AF: 0.873 AC: 4506 AN: 5164

South Asian (SAS) AF: 0.671 AC: 3230 AN: 4814

European-Finnish (FIN) AF: 0.722 AC: 7607 AN: 10536

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.653 AC: 44370 AN: 67964

Other (OTH) AF: 0.657 AC: 1384 AN: 2108

Alfa AF: 0.636 Hom.: 14384

Bravo AF: 0.649

Asia WGS AF: 0.788 AC: 2735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.78
PhyloP100		-0.15
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: rs822395; hg19: chr3-186566807;