NM_004797.4:c.-9+359C>T

Variant names:

• chr3-186843108-C-T
• rs62292784
• NM_004797.4:c.-9+359C>T

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+359C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,082 control chromosomes in the GnomAD database, including 4,340 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 0.23 (4340 hom., cov: 32)
• Consequence: ADIPOQ NM_004797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOQ	NM_004797.4	MANE Select	c.-9+359C>T		intron	N/A	NP_004788.1
	ADIPOQ	NM_001177800.2		c.-60+359C>T		intron	N/A	NP_001171271.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOQ	ENST00000320741.7	TSL:1 MANE Select	c.-9+359C>T		intron	N/A	ENSP00000320709.2
	ADIPOQ	ENST00000444204.2	TSL:1	c.-60+359C>T		intron	N/A	ENSP00000389814.2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34242 AN: 151964 Hom.: 4340 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.225 AC: 34254 AN: 152082 Hom.: 4340 Cov.: 32 AF XY: 0.228 AC XY: 16974 AN XY: 74354

African (AFR) AF: 0.118 AC: 4885 AN: 41496

American (AMR) AF: 0.250 AC: 3815 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 982 AN: 3472

East Asian (EAS) AF: 0.259 AC: 1340 AN: 5170

South Asian (SAS) AF: 0.272 AC: 1308 AN: 4814

European-Finnish (FIN) AF: 0.322 AC: 3404 AN: 10576

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17554 AN: 67978

Other (OTH) AF: 0.217 AC: 458 AN: 2108

Alfa AF: 0.249 Hom.: 2046

Bravo AF: 0.219

Asia WGS AF: 0.268 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.54
PhyloP100		0.15
PromoterAI		0.0028	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs62292784; hg19: chr3-186560897;