NM_004797.4:c.-8-4033C>A

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The NM_004797.4(ADIPOQ):c.-8-4033C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene ADIPOQ is a tumor suppressor gene (CancerMine: 2 TSG, 6 oncogene citations). The gene ADIPOQ is a known oncogene (CancerMine: 2 TSG, 6 oncogene citations). The variant allele was found at a cumulative frequency of 0.652 (AC=99,010) in the gnomAD database across 151,928 control chromosomes, including 32,601 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.851. 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 0.65 (32601 hom., cov: 31)
• Consequence: ADIPOQ NM_004797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 62 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 ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.851 — exceeds 1% threshold (B1 applied)

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>A	intron	Intron 1 of 2	Prot: NP_004788.1 UniProt:
	ADIPOQ NM_001177800.2		c.-9+3411C>A	intron	Intron 2 of 3	Prot: NP_001171271.1 UniProt:

ADIPOQ NM_004797.4

MANE Select

HGVSc / HGVSpc.-8-4033C>A

Exon rankIntron 1 of 2

intron

Prot: NP_004788.1UniProt: Q15848A8K660

ADIPOQ NM_001177800.2

HGVSc / HGVSpc.-9+3411C>A

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>A	intron	Intron 1 of 2	Prot: ENSP00000320709.2 UniProt:
	ADIPOQ ENST00000444204.2	TSL:1	c.-9+3411C>A	intron	Intron 2 of 3	Prot: ENSP00000389814.2 UniProt:
	ADIPOQ ENST00000881747.1		c.-9+3411C>A	intron	Intron 1 of 2	Prot: ENSP00000551806.1 UniProt:

ADIPOQ ENST00000320741.7

TSL:1MANE Select

HGVSc / HGVSpc.-8-4033C>A

Exon rankIntron 1 of 2

intron

Prot: ENSP00000320709.2UniProt: Q15848

ADIPOQ ENST00000444204.2

TSL:1

HGVSc / HGVSpc.-9+3411C>A

Exon rankIntron 2 of 3

intron

Prot: ENSP00000389814.2UniProt: Q15848

ADIPOQ ENST00000881747.1

HGVSc / HGVSpc.-9+3411C>A

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: 0.652	AC:98932	Hom:32567	AN:151810	Cov:31
GnomAD4 genome	AF: 0.652	AC:99010	Hom:32601	AN:151928	Cov:31
TOPMed (Bravo)	AF: 0.649	AC:171820	Hom:56367	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.631	AC:59007	Hom:19021	AN:93446	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.646	AC:1512	Hom:497	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.862	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.720	AC:216	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.788	AC:2735	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.905	AC:6544	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.705	AC:124	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.942	AC:115659	Hom:54489	AN:122792	Cov:
Turkish Variome	AF: 0.678	AC:1047	Hom:357	AN:1544	Cov:
UK10K	AF: 0.638	AC:4826	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.855	AC:7659	Hom:3278	AN:8960	Cov:

Showing 14 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	5.1
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.78
GPN-Star LLR	N/A	0.16
GPN-Star score	N/A	-0.16
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-0.15

Showing 8 of 8 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