3-186849018-C-G

Variant names:

• chr3-186849018-C-G
• rs822395
• NM_004797.4:c.-8-4033C>G

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-3 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -3 classification points (ACMG Germline Pathogenicity v2019). PM2_SupportingBP4_Strong

The NM_004797.4(ADIPOQ):c.-8-4033C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.0000263 (AC=4) in the gnomAD database across 151,880 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.0000326. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000026 (0 hom., cov: 31)
• Consequence: ADIPOQ NM_004797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 15 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)

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -3 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Rare in gnomAD for AD/XL gene (popmax AF below threshold) — PM2 Supporting; GnomAD popmax AF = 0.0000326 — borderline rare for AD/XL gene (threshold 0.0001) — PM2 supporting.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_004797.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ADIPOQ NM_004797.4	MANE Select	c.-8-4033C>G	intron	Intron 1 of 2	Prot: NP_004788.1 UniProt:
	ADIPOQ NM_001177800.2		c.-9+3411C>G	intron	Intron 2 of 3	Prot: NP_001171271.1 UniProt:

ADIPOQ NM_004797.4

MANE Select

HGVSc / HGVSpc.-8-4033C>G

Exon rankIntron 1 of 2

intron

Prot: NP_004788.1UniProt: Q15848A8K660

ADIPOQ NM_001177800.2

HGVSc / HGVSpc.-9+3411C>G

Exon rankIntron 2 of 3

intron

Prot: NP_001171271.1UniProt: A8K660Q15848

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ADIPOQ ENST00000320741.7	TSL:1MANE Select	c.-8-4033C>G	intron	Intron 1 of 2	Prot: ENSP00000320709.2 UniProt:
	ADIPOQ ENST00000444204.2	TSL:1	c.-9+3411C>G	intron	Intron 2 of 3	Prot: ENSP00000389814.2 UniProt:
	ADIPOQ ENST00000881747.1		c.-9+3411C>G	intron	Intron 1 of 2	Prot: ENSP00000551806.1 UniProt:

ADIPOQ ENST00000320741.7

TSL:1MANE Select

HGVSc / HGVSpc.-8-4033C>G

Exon rankIntron 1 of 2

intron

Prot: ENSP00000320709.2UniProt: Q15848

ADIPOQ ENST00000444204.2

TSL:1

HGVSc / HGVSpc.-9+3411C>G

Exon rankIntron 2 of 3

intron

Prot: ENSP00000389814.2UniProt: Q15848

ADIPOQ ENST00000881747.1

HGVSc / HGVSpc.-9+3411C>G

Exon rankIntron 1 of 2

intron

Prot: ENSP00000551806.1UniProt: Q15848

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.0000263	AC:4	Hom:0	AN:151880	Cov:31
GnomAD4 genome	AF: 0.0000263	AC:4	Hom:0	AN:151880	Cov:31
TOPMed (Bravo) Warning	AF: 0.0000453	AC:12	Hom:2	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:19021	AN:93446	Cov:

Showing 4 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	4.9
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.67
GPN-Star LLR	N/A	0.13
GPN-Star score	N/A	-0.13
PhyloP100	Benign	-0.15

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs822395;

hg19: chr3-186566807;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar