rs7649121

Positions:

• chr3-186850996-A-T

Variant summary

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

The NM_004797.4(ADIPOQ):​c.-8-2055A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,004 control chromosomes in the GnomAD database, including 2,279 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 0.17 (2279 hom., cov: 31)
• Consequence: ADIPOQ NM_004797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADIPOQ	NM_004797.4	c.-8-2055A>T		intron_variant		ENST00000320741.7	NP_004788.1
ADIPOQ	NM_001177800.2	c.-8-2055A>T		intron_variant			NP_001171271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADIPOQ	ENST00000320741.7	c.-8-2055A>T		intron_variant		1	NM_004797.4	ENSP00000320709	P1
ADIPOQ	ENST00000444204.2	c.-8-2055A>T		intron_variant		1		ENSP00000389814	P1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25746 AN: 151886 Hom.: 2276 Cov.: 31

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.144

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.169 AC: 25760 AN: 152004 Hom.: 2279 Cov.: 31 AF XY: 0.172 AC XY: 12742 AN XY: 74292

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.164

Alfa AF: 0.176 Hom.: 297

Bravo AF: 0.171

Asia WGS AF: 0.217 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.60
DANN	Benign	0.65

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: rs7649121; hg19: chr3-186568785;