rs3774261

Variant names:

• chr3-186853770-A-G
• rs3774261
• NM_004797.4:c.215-414A>G

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_004797.4(ADIPOQ):c.215-414A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.56 (AC=122,673) in the gnomAD database across 219,150 control chromosomes, including 35,445 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.627. 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 0.55 (23347 hom., cov: 29)
  • Exomes 𝑓: 0.59 (12098 hom.)
• Consequence: ADIPOQ NM_004797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 6 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)

ADIPOQ-AS1 (HGNC:40648): ()

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	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).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.6275 — exceeds 5%% threshold (BA1 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.215-414A>G	intron	Intron 2 of 2	Prot: NP_004788.1 UniProt:
	ADIPOQ NM_001177800.2		c.215-414A>G	intron	Intron 3 of 3	Prot: NP_001171271.1 UniProt:
	ADIPOQ-AS1 NR_046662.2		n.2215+8T>C	splice_regionintron	Intron 3 of 3	Prot:

ADIPOQ NM_004797.4

MANE Select

HGVSc / HGVSpc.215-414A>G

Exon rankIntron 2 of 2

intron

Prot: NP_004788.1UniProt: Q15848A8K660

ADIPOQ NM_001177800.2

HGVSc / HGVSpc.215-414A>G

Exon rankIntron 3 of 3

intron

Prot: NP_001171271.1UniProt: A8K660Q15848

ADIPOQ-AS1 NR_046662.2

HGVSc / HGVSpn.2215+8T>C

Exon rankIntron 3 of 3

splice_regionintron

Prot:

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ADIPOQ ENST00000320741.7	TSL:1MANE Select	c.215-414A>G	intron	Intron 2 of 2	Prot: ENSP00000320709.2 UniProt:
	ADIPOQ ENST00000444204.2	TSL:1	c.215-414A>G	intron	Intron 3 of 3	Prot: ENSP00000389814.2 UniProt:
	ADIPOQ ENST00000881747.1		c.215-414A>G	intron	Intron 2 of 2	Prot: ENSP00000551806.1 UniProt:

ADIPOQ ENST00000320741.7

TSL:1MANE Select

HGVSc / HGVSpc.215-414A>G

Exon rankIntron 2 of 2

intron

Prot: ENSP00000320709.2UniProt: Q15848

ADIPOQ ENST00000444204.2

TSL:1

HGVSc / HGVSpc.215-414A>G

Exon rankIntron 3 of 3

intron

Prot: ENSP00000389814.2UniProt: Q15848

ADIPOQ ENST00000881747.1

HGVSc / HGVSpc.215-414A>G

Exon rankIntron 2 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 5 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.548	AC:82958	Hom:23333	AN:151318	Cov:29
GnomAD4 exome	AF: 0.586	AC:39679	Hom:12098	AN:67714	Cov:0
GnomAD4 genome	AF: 0.548	AC:82994	Hom:23347	AN:151436	Cov:29
TOPMed (Bravo)	AF: 0.534	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.590	AC:129586	Hom:38758	AN:219528	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.518	AC:1213	Hom:311	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.441	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.600	AC:180	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.495	AC:1721	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.409	AC:2959	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.420	AC:74	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.410	AC:50332	Hom:10410	AN:122732	Cov:
Turkish Variome	AF: 0.563	AC:869	Hom:251	AN:1544	Cov:
UK10K	AF: 0.625	AC:4728	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.439	AC:3937	Hom:870	AN:8960	Cov:

Showing 15 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.250	6361	25492	0.176	6146	34844

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	1.2
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.57
DANN	Benign	0.52
GPN-Star LLR	N/A	3.7
GPN-Star score	N/A	0.19
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	0.0070

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: rs3774261;

hg19: chr3-186571559;

COSMIC: COSV57860260;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar