3-186846014-C-T

Variant names:

• chr3-186846014-C-T
• rs822391
• NM_004797.4:c.-9+3265C>T

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+3265C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 152,100 control chromosomes in the GnomAD database, including 55,365 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 0.85 (55365 hom., cov: 30)
• Consequence: ADIPOQ NM_004797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 30 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 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.-9+3265C>T		intron	N/A	NP_004788.1	Q15848
	ADIPOQ	NM_001177800.2		c.-9+407C>T		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.-9+3265C>T		intron	N/A	ENSP00000320709.2	Q15848
	ADIPOQ	ENST00000444204.2	TSL:1	c.-9+407C>T		intron	N/A	ENSP00000389814.2	Q15848
	ADIPOQ	ENST00000881747.1		c.-9+407C>T		intron	N/A	ENSP00000551806.1

Frequencies

GnomAD3 genomes AF: 0.850 AC: 129177 AN: 151982 Hom.: 55293 Cov.: 30

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.845

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.855

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

GnomAD4 genome AF: 0.850 AC: 129312 AN: 152100 Hom.: 55365 Cov.: 30 AF XY: 0.849 AC XY: 63108 AN XY: 74346

African (AFR) AF: 0.959 AC: 39829 AN: 41516

American (AMR) AF: 0.846 AC: 12926 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2960 AN: 3472

East Asian (EAS) AF: 0.888 AC: 4591 AN: 5170

South Asian (SAS) AF: 0.796 AC: 3833 AN: 4816

European-Finnish (FIN) AF: 0.799 AC: 8432 AN: 10558

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.794 AC: 53973 AN: 67966

Other (OTH) AF: 0.857 AC: 1811 AN: 2114

Alfa AF: 0.818 Hom.: 80540

Bravo AF: 0.860

Asia WGS AF: 0.885 AC: 3079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.86
DANN	Benign	0.62
PhyloP100		-0.43
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: rs822391; hg19: chr3-186563803;