rs7649121

Variant names:

• chr3-186850996-A-T
• rs7649121
• NM_004797.4:c.-8-2055A>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.-8-2055A>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
• Publications: 43 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 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.-8-2055A>T		intron	N/A	NP_004788.1
	ADIPOQ	NM_001177800.2		c.-8-2055A>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.-8-2055A>T		intron	N/A	ENSP00000320709.2
	ADIPOQ	ENST00000444204.2	TSL:1	c.-8-2055A>T		intron	N/A	ENSP00000389814.2

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

African (AFR) AF: 0.123 AC: 5107 AN: 41486

American (AMR) AF: 0.194 AC: 2959 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1232 AN: 5172

South Asian (SAS) AF: 0.167 AC: 806 AN: 4814

European-Finnish (FIN) AF: 0.220 AC: 2327 AN: 10554

Middle Eastern (MID) AF: 0.155 AC: 45 AN: 290

European-Non Finnish (NFE) AF: 0.176 AC: 11967 AN: 67930

Other (OTH) AF: 0.164 AC: 346 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.60
DANN	Benign	0.65
PhyloP100		-0.23
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: rs7649121; hg19: chr3-186568785;