rs16861210

Variant names:

• chr3-186848709-G-A
• rs16861210
• NM_004797.4:c.-8-4342G>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.-8-4342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,188 control chromosomes in the GnomAD database, including 1,050 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 0.10 (1050 hom., cov: 32)
• Consequence: ADIPOQ NM_004797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.704
• Publications: 21 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOQ	NM_004797.4	c.-8-4342G>A		intron_variant	Intron 1 of 2	ENST00000320741.7	NP_004788.1
ADIPOQ	NM_001177800.2	c.-9+3102G>A		intron_variant	Intron 2 of 3		NP_001171271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADIPOQ	ENST00000320741.7	c.-8-4342G>A		intron_variant	Intron 1 of 2	1	NM_004797.4	ENSP00000320709.2
ADIPOQ	ENST00000444204.2	c.-9+3102G>A		intron_variant	Intron 2 of 3	1		ENSP00000389814.2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15773 AN: 152070 Hom.: 1043 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0916

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.0259

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0889

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.104 AC: 15801 AN: 152188 Hom.: 1050 Cov.: 32 AF XY: 0.0998 AC XY: 7428 AN XY: 74432

African (AFR) AF: 0.175 AC: 7252 AN: 41502

American (AMR) AF: 0.0914 AC: 1398 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 403 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.0191 AC: 92 AN: 4828

European-Finnish (FIN) AF: 0.0259 AC: 274 AN: 10596

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0889 AC: 6041 AN: 67990

Other (OTH) AF: 0.117 AC: 248 AN: 2114

Alfa AF: 0.0938 Hom.: 1065

Bravo AF: 0.115

Asia WGS AF: 0.0260 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.89
PhyloP100		-0.70
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: rs16861210; hg19: chr3-186566498;