3-186848537-C-T

Variant names:

• chr3-186848537-C-T
• rs822393
• NM_004797.4:c.-8-4514C>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.-8-4514C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,980 control chromosomes in the GnomAD database, including 7,499 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 0.30 (7499 hom., cov: 31)
• Consequence: ADIPOQ NM_004797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135
• Publications: 35 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 (EAS) allele frequency at 95% confidence interval = 0.459 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.-8-4514C>T		intron	N/A	NP_004788.1	Q15848
	ADIPOQ	NM_001177800.2		c.-9+2930C>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.-8-4514C>T		intron	N/A	ENSP00000320709.2	Q15848
	ADIPOQ	ENST00000444204.2	TSL:1	c.-9+2930C>T		intron	N/A	ENSP00000389814.2	Q15848
	ADIPOQ	ENST00000881747.1		c.-9+2930C>T		intron	N/A	ENSP00000551806.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46094 AN: 151862 Hom.: 7488 Cov.: 31

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.304 AC: 46139 AN: 151980 Hom.: 7499 Cov.: 31 AF XY: 0.312 AC XY: 23169 AN XY: 74268

African (AFR) AF: 0.344 AC: 14273 AN: 41452

American (AMR) AF: 0.344 AC: 5249 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 906 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2447 AN: 5154

South Asian (SAS) AF: 0.232 AC: 1115 AN: 4812

European-Finnish (FIN) AF: 0.439 AC: 4623 AN: 10528

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.244 AC: 16554 AN: 67972

Other (OTH) AF: 0.276 AC: 583 AN: 2112

Alfa AF: 0.282 Hom.: 787

Bravo AF: 0.303

Asia WGS AF: 0.378 AC: 1315 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	7.5
DANN	Benign	0.82
PhyloP100		0.14
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: rs822393; hg19: chr3-186566326;