rs4686804

Variant names:

• chr3-186856697-G-A
• rs4686804
• NM_004797.4:c.*1993G>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.*1993G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,804 control chromosomes in the GnomAD database, including 19,669 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 0.50 (19669 hom., cov: 31)
  • Exomes 𝑓: 0.58 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADIPOQ NM_004797.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 9 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-AS1 (HGNC:40648): (ADIPOQ antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.556 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.*1993G>A		3_prime_UTR	Exon 3 of 3	NP_004788.1	Q15848
	ADIPOQ	NM_001177800.2		c.*1993G>A		3_prime_UTR	Exon 4 of 4	NP_001171271.1	A8K660
	ADIPOQ-AS1	NR_046662.2		n.137-581C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOQ	ENST00000320741.7	TSL:1 MANE Select	c.*1993G>A		3_prime_UTR	Exon 3 of 3	ENSP00000320709.2	Q15848
	ADIPOQ	ENST00000444204.2	TSL:1	c.*1993G>A		3_prime_UTR	Exon 4 of 4	ENSP00000389814.2	Q15848
	ADIPOQ	ENST00000881747.1		c.*1993G>A		3_prime_UTR	Exon 3 of 3	ENSP00000551806.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76492 AN: 151682 Hom.: 19657 Cov.: 31

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.472

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.583 AC: 7 AN: 12 Hom.: 3 Cov.: 0 AF XY: 0.750 AC XY: 6 AN XY: 8

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.625 AC: 5 AN: 8

Other (OTH) AF: 1.00 AC: 2 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.504 AC: 76527 AN: 151804 Hom.: 19669 Cov.: 31 AF XY: 0.502 AC XY: 37229 AN XY: 74198

African (AFR) AF: 0.425 AC: 17563 AN: 41354

American (AMR) AF: 0.459 AC: 6992 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1627 AN: 3468

East Asian (EAS) AF: 0.398 AC: 2057 AN: 5166

South Asian (SAS) AF: 0.560 AC: 2691 AN: 4802

European-Finnish (FIN) AF: 0.557 AC: 5868 AN: 10530

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38075 AN: 67924

Other (OTH) AF: 0.471 AC: 994 AN: 2112

Alfa AF: 0.538 Hom.: 2919

Bravo AF: 0.497

Asia WGS AF: 0.443 AC: 1541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.41
DANN	Benign	0.55
PhyloP100		0.019
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4686804;

hg19: chr3-186574486;