rs3745367

Positions:

• chr19-7669625-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RETN	NM_020415.4	c.118+181G>A		intron_variant		ENST00000221515.6	NP_065148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RETN	ENST00000221515.6	c.118+181G>A		intron_variant		1	NM_020415.4	ENSP00000221515	P1
RETN	ENST00000381324.2	c.118+181G>A		intron_variant		1		ENSP00000370725
RETN	ENST00000629642.1	c.118+181G>A		intron_variant		5		ENSP00000485998

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

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.360

Alfa AF: 0.268 Hom.: 11265

Bravo AF: 0.398

Asia WGS AF: 0.358 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.66

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: rs3745367; hg19: chr19-7734511;