rs16861205

Variant names:

• chr3-186843845-G-A
• rs16861205
• NM_004797.4:c.-9+1096G>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.-9+1096G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,024 control chromosomes in the GnomAD database, including 1,699 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 0.13 (1699 hom., cov: 30)
• Consequence: ADIPOQ NM_004797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 44 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOQ	NM_004797.4	c.-9+1096G>A		intron_variant	Intron 1 of 2	ENST00000320741.7	NP_004788.1
ADIPOQ	NM_001177800.2	c.-60+1096G>A		intron_variant	Intron 1 of 3		NP_001171271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADIPOQ	ENST00000320741.7	c.-9+1096G>A		intron_variant	Intron 1 of 2	1	NM_004797.4	ENSP00000320709.2
ADIPOQ	ENST00000444204.2	c.-60+1096G>A		intron_variant	Intron 1 of 3	1		ENSP00000389814.2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20293 AN: 151908 Hom.: 1689 Cov.: 30

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.0634

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0767

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.134 AC: 20323 AN: 152024 Hom.: 1699 Cov.: 30 AF XY: 0.140 AC XY: 10421 AN XY: 74288

African (AFR) AF: 0.208 AC: 8623 AN: 41440

American (AMR) AF: 0.156 AC: 2379 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 229 AN: 3470

East Asian (EAS) AF: 0.175 AC: 904 AN: 5168

South Asian (SAS) AF: 0.0626 AC: 302 AN: 4826

European-Finnish (FIN) AF: 0.221 AC: 2329 AN: 10538

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0766 AC: 5211 AN: 67986

Other (OTH) AF: 0.114 AC: 240 AN: 2112

Alfa AF: 0.0895 Hom.: 399

Bravo AF: 0.130

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.3
DANN	Benign	0.78
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs16861205; hg19: chr3-186561634;