3-186853079-TCTA-T

Variant names:

• chr3-186853079-TCTA-T
• rs547607723
• NM_004797.4:c.24_26delACT

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 2 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-AS1 (HGNC:40648): (ADIPOQ antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -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 Homozygotes in GnomAdExome4 at 8 Unknown gene

Transcripts

RefSeq

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

Ensembl

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

GnomAD2 exomes AF: 0.000870 AC: 218 AN: 250716 AF XY: 0.00114

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 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

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.000380 AC: 17 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00467 AC: 403 AN: 86258

European-Finnish (FIN) AF: 0.000318 AC: 17 AN: 53420

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.000330 AC: 367 AN: 1112004

Other (OTH) AF: 0.000762 AC: 46 AN: 60396

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

African (AFR) AF: 0.0000481 AC: 2 AN: 41564

American (AMR) AF: 0.000196 AC: 3 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4824

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68016

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

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

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.3
Mutation Taster		=75/25	polymorphism

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: rs547607723; hg19: chr3-186570868;