chr3-186854025-G-A

Variant names:

• chr3-186854025-G-A
• rs3774262
• NM_004797.4:c.215-159G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004797.4(ADIPOQ):​c.215-159G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 687,612 control chromosomes in the GnomAD database, including 6,065 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 0.10 (1105 hom., cov: 31)
  • Exomes 𝑓: 0.12 (4960 hom.)
• Consequence: ADIPOQ NM_004797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335
• Publications: 39 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: 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 = 0.278 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.215-159G>A		intron	N/A	NP_004788.1
	ADIPOQ	NM_001177800.2		c.215-159G>A		intron	N/A	NP_001171271.1
	ADIPOQ-AS1	NR_046662.2		n.2120+108C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOQ	ENST00000320741.7	TSL:1 MANE Select	c.215-159G>A		intron	N/A	ENSP00000320709.2
	ADIPOQ	ENST00000444204.2	TSL:1	c.215-159G>A		intron	N/A	ENSP00000389814.2
	ADIPOQ-AS1	ENST00000422718.1	TSL:5	n.1991+108C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15886 AN: 151938 Hom.: 1106 Cov.: 31

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0432

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.122 AC: 65116 AN: 535556 Hom.: 4960 Cov.: 7 AF XY: 0.122 AC XY: 33926 AN XY: 277254

African (AFR) AF: 0.0428 AC: 594 AN: 13868

American (AMR) AF: 0.176 AC: 3237 AN: 18384

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 2826 AN: 14102

East Asian (EAS) AF: 0.293 AC: 9191 AN: 31398

South Asian (SAS) AF: 0.126 AC: 5429 AN: 43160

European-Finnish (FIN) AF: 0.0445 AC: 1663 AN: 37382

Middle Eastern (MID) AF: 0.209 AC: 460 AN: 2202

European-Non Finnish (NFE) AF: 0.109 AC: 37825 AN: 346338

Other (OTH) AF: 0.135 AC: 3891 AN: 28722

GnomAD4 genome AF: 0.105 AC: 15896 AN: 152056 Hom.: 1105 Cov.: 31 AF XY: 0.107 AC XY: 7930 AN XY: 74332

African (AFR) AF: 0.0469 AC: 1945 AN: 41504

American (AMR) AF: 0.182 AC: 2783 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 699 AN: 3458

East Asian (EAS) AF: 0.290 AC: 1498 AN: 5162

South Asian (SAS) AF: 0.131 AC: 631 AN: 4810

European-Finnish (FIN) AF: 0.0432 AC: 457 AN: 10572

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.109 AC: 7401 AN: 67972

Other (OTH) AF: 0.163 AC: 343 AN: 2110

Alfa AF: 0.116 Hom.: 3057

Bravo AF: 0.113

Asia WGS AF: 0.207 AC: 719 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	6.6
DANN	Benign	0.34
PhyloP100		0.34
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: rs3774262; hg19: chr3-186571814; COSMIC: COSV57860255;