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

Variant names:

• chr3-186849018-C-G
• rs822395
• NM_004797.4:c.-8-4033C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004797.4(ADIPOQ):​c.-8-4033C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 151,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000026 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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>G		intron	N/A	NP_004788.1	Q15848
	ADIPOQ	NM_001177800.2		c.-9+3411C>G		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>G		intron	N/A	ENSP00000320709.2	Q15848
	ADIPOQ	ENST00000444204.2	TSL:1	c.-9+3411C>G		intron	N/A	ENSP00000389814.2	Q15848
	ADIPOQ	ENST00000881747.1		c.-9+3411C>G		intron	N/A	ENSP00000551806.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151880 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000969

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151880 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74156

African (AFR) AF: 0.0000969 AC: 4 AN: 41298

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 14384

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.67
PhyloP100		-0.15

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;