19-7669625-G-A

Variant names:

• chr19-7669625-G-A
• rs3745367
• NM_020415.4:c.118+181G>A

Variant summary

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

The NM_020415.4(RETN):​c.118+181G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 151,664 control chromosomes in the GnomAD database, including 14,380 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 0.38 (14380 hom., cov: 30)
• Consequence: RETN NM_020415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• Publications: 110 publications found

Genes affected

RETN (HGNC:20389): (resistin) This gene belongs to the family defined by the mouse resistin-like genes. The characteristic feature of this family is the C-terminal stretch of 10 cys residues with identical spacing. The mouse homolog of this protein is secreted by adipocytes, and may be the hormone potentially linking obesity to type II diabetes. The encoded protein also has an antimicrobial role in skin, displaying antibacterial activity against both Gram positive and Gram negative bacteria. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2020]

RETN Gene-Disease associations (from GenCC):

• diabetes mellitus, noninsulin-dependent

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020415.4. 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
	RETN	NM_020415.4	MANE Select	c.118+181G>A		intron	N/A	NP_065148.1
	RETN	NM_001385726.1		c.118+181G>A		intron	N/A	NP_001372655.1
	RETN	NM_001193374.2		c.118+181G>A		intron	N/A	NP_001180303.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETN	ENST00000221515.6	TSL:1 MANE Select	c.118+181G>A		intron	N/A	ENSP00000221515.1
	RETN	ENST00000381324.2	TSL:1	c.118+181G>A		intron	N/A	ENSP00000370725.2
	RETN	ENST00000629642.1	TSL:5	c.118+181G>A		intron	N/A	ENSP00000485998.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58271 AN: 151544 Hom.: 14344 Cov.: 30

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.385 AC: 58355 AN: 151664 Hom.: 14380 Cov.: 30 AF XY: 0.384 AC XY: 28431 AN XY: 74100

African (AFR) AF: 0.710 AC: 29372 AN: 41370

American (AMR) AF: 0.272 AC: 4140 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1030 AN: 3466

East Asian (EAS) AF: 0.363 AC: 1853 AN: 5108

South Asian (SAS) AF: 0.385 AC: 1847 AN: 4802

European-Finnish (FIN) AF: 0.249 AC: 2615 AN: 10520

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16470 AN: 67860

Other (OTH) AF: 0.360 AC: 758 AN: 2108

Alfa AF: 0.288 Hom.: 30479

Bravo AF: 0.398

Asia WGS AF: 0.358 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.66
PhyloP100		-0.21
PromoterAI		0.010	Neutral
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: rs3745367; hg19: chr19-7734511;