rs3774261

Positions:

• chr3-186853770-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000320741.7(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 frequency of 0.56 in 219,150 control chromosomes in the GnomAD database, including 35,445 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 0.55 (23347 hom., cov: 29)
  • Exomes 𝑓: 0.59 (12098 hom.)
• Consequence: ADIPOQ ENST00000320741.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

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-AS1 (HGNC:40648): (ADIPOQ antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADIPOQ	NM_004797.4	c.215-414A>G		intron_variant		ENST00000320741.7	NP_004788.1
ADIPOQ-AS1	NR_046662.2	n.2215+8T>C		splice_region_variant, intron_variant, non_coding_transcript_variant
ADIPOQ	NM_001177800.2	c.215-414A>G		intron_variant			NP_001171271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADIPOQ	ENST00000320741.7	c.215-414A>G		intron_variant		1	NM_004797.4	ENSP00000320709	P1
ADIPOQ	ENST00000444204.2	c.215-414A>G		intron_variant		1		ENSP00000389814	P1
ADIPOQ-AS1	ENST00000422718.1	n.2086+8T>C		splice_region_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.548 AC: 82958 AN: 151318 Hom.: 23333 Cov.: 29

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.511

GnomAD4 exome AF: 0.586 AC: 39679 AN: 67714 Hom.: 12098 Cov.: 0 AF XY: 0.586 AC XY: 20350 AN XY: 34714

Gnomad4 AFR exome AF: 0.415

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.472

Gnomad4 EAS exome AF: 0.404

Gnomad4 SAS exome AF: 0.644

Gnomad4 FIN exome AF: 0.626

Gnomad4 NFE exome AF: 0.613

Gnomad4 OTH exome AF: 0.572

GnomAD4 genome AF: 0.548 AC: 82994 AN: 151436 Hom.: 23347 Cov.: 29 AF XY: 0.548 AC XY: 40476 AN XY: 73924

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.511

Alfa AF: 0.585 Hom.: 4444

Bravo AF: 0.534

Asia WGS AF: 0.495 AC: 1721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.57
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs3774261; hg19: chr3-186571559; COSMIC: COSV57860260;