3-186853079-TCTA-T

Position:

• chr3-186853079-TCTA-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_Supporting BP6_Moderate BS2

The NM_004797.4(ADIPOQ):​c.24_26delACT​(p.Leu9del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000577 in 1,614,180 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00060 (8 hom.)
• Consequence: ADIPOQ NM_004797.4 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.25

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:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_004797.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 3-186853079-TCTA-T is Benign according to our data. Variant chr3-186853079-TCTA-T is described in ClinVar as [Likely_benign]. Clinvar id is 721271.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 59 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADIPOQ	NM_004797.4	c.24_26delACT	p.Leu9del	disruptive_inframe_deletion	2/3	ENST00000320741.7	NP_004788.1
ADIPOQ	NM_001177800.2	c.24_26delACT	p.Leu9del	disruptive_inframe_deletion	3/4		NP_001171271.1
ADIPOQ-AS1	NR_046662.2	n.2376_2378delTAG		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADIPOQ	ENST00000320741.7	c.24_26delACT	p.Leu9del	disruptive_inframe_deletion	2/3	1	NM_004797.4	ENSP00000320709.2
ADIPOQ	ENST00000444204.2	c.24_26delACT	p.Leu9del	disruptive_inframe_deletion	3/4	1		ENSP00000389814.2
ADIPOQ-AS1	ENST00000422718.1	n.2247_2249delTAG		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.000388 AC: 59 AN: 152178 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000870 AC: 218 AN: 250716 Hom.: 2 AF XY: 0.00114 AC XY: 154 AN XY: 135558

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00441

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.000557

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000597 AC: 873 AN: 1461884 Hom.: 8 AF XY: 0.000760 AC XY: 553 AN XY: 727246

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000380

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00467

Gnomad4 FIN exome AF: 0.000318

Gnomad4 NFE exome AF: 0.000330

Gnomad4 OTH exome AF: 0.000762

GnomAD4 genome AF: 0.000387 AC: 59 AN: 152296 Hom.: 0 Cov.: 33 AF XY: 0.000416 AC XY: 31 AN XY: 74460

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000158 Hom.: 0

Bravo AF: 0.000363

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000981

EpiControl AF: 0.000889

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs547607723; hg19: chr3-186570868;