rs3745368

Positions:

• chr19-7670411-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.*62G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 1,506,650 control chromosomes in the GnomAD database, including 1,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.065 (467 hom., cov: 31)
  • Exomes 𝑓: 0.040 (1447 hom.)
• Consequence: RETN NM_020415.4 3_prime_UTR
• Clinical Significance: risk factor no assertion criteria provided O:2
• Conservation: PhyloP100: -0.905

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RETN	NM_020415.4	c.*62G>A		3_prime_UTR_variant	4/4	ENST00000221515.6	NP_065148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RETN	ENST00000221515.6	c.*62G>A		3_prime_UTR_variant	4/4	1	NM_020415.4	ENSP00000221515	P1
RETN	ENST00000629642.1	c.*62G>A		3_prime_UTR_variant	3/3	5		ENSP00000485998

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9673 AN: 149496 Hom.: 460 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0113

Gnomad AMR AF: 0.0468

Gnomad ASJ AF: 0.00812

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.0490

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.0349

Gnomad OTH AF: 0.0606

GnomAD4 exome AF: 0.0396 AC: 53792 AN: 1357038 Hom.: 1447 Cov.: 30 AF XY: 0.0391 AC XY: 26084 AN XY: 667812

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.0279

Gnomad4 ASJ exome AF: 0.00904

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.0386

Gnomad4 FIN exome AF: 0.0202

Gnomad4 NFE exome AF: 0.0359

Gnomad4 OTH exome AF: 0.0466

GnomAD4 genome AF: 0.0649 AC: 9711 AN: 149612 Hom.: 467 Cov.: 31 AF XY: 0.0639 AC XY: 4667 AN XY: 72986

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0468

Gnomad4 ASJ AF: 0.00812

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.0488

Gnomad4 FIN AF: 0.0210

Gnomad4 NFE AF: 0.0349

Gnomad4 OTH AF: 0.0604

Alfa AF: 0.0497 Hom.: 74

Bravo AF: 0.0694

Asia WGS AF: 0.0840 AC: 294 AN: 3476

ClinVar

Significance: risk factor

Submissions summary: Other:2

Revision: no assertion criteria provided

Submissions by phenotype

Diabetes mellitus type 2, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2003

- -

HYPERTENSION, INSULIN RESISTANCE-RELATED, SUSCEPTIBILITY TO Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Mar 01, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.90

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: rs3745368; hg19: chr19-7735297;