3-186850391-G-T

Variant names:

• chr3-186850391-G-T
• rs12495941
• NM_004797.4:c.-8-2660G>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.-8-2660G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,702 control chromosomes in the GnomAD database, including 9,420 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 0.35 (9420 hom., cov: 30)
• Consequence: ADIPOQ NM_004797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 54 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOQ	NM_004797.4	c.-8-2660G>T		intron_variant	Intron 1 of 2	ENST00000320741.7	NP_004788.1
ADIPOQ	NM_001177800.2	c.-8-2660G>T		intron_variant	Intron 2 of 3		NP_001171271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADIPOQ	ENST00000320741.7	c.-8-2660G>T		intron_variant	Intron 1 of 2	1	NM_004797.4	ENSP00000320709.2
ADIPOQ	ENST00000444204.2	c.-8-2660G>T		intron_variant	Intron 2 of 3	1		ENSP00000389814.2

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52808 AN: 151592 Hom.: 9413 Cov.: 30

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.348 AC: 52847 AN: 151702 Hom.: 9420 Cov.: 30 AF XY: 0.345 AC XY: 25543 AN XY: 74118

African (AFR) AF: 0.355 AC: 14652 AN: 41324

American (AMR) AF: 0.356 AC: 5419 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1329 AN: 3470

East Asian (EAS) AF: 0.399 AC: 2057 AN: 5156

South Asian (SAS) AF: 0.431 AC: 2071 AN: 4802

European-Finnish (FIN) AF: 0.230 AC: 2410 AN: 10478

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23776 AN: 67926

Other (OTH) AF: 0.377 AC: 793 AN: 2102

Alfa AF: 0.349 Hom.: 8856

Bravo AF: 0.354

Asia WGS AF: 0.404 AC: 1403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.75
PhyloP100		-0.15
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: rs12495941; hg19: chr3-186568180;