19-7670411-G-A

Variant names:

• chr19-7670411-G-A
• rs3745368
• NM_020415.4:c.*62G>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.*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
• Publications: 40 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETN	NM_020415.4	MANE Select	c.*62G>A		3_prime_UTR	Exon 4 of 4	NP_065148.1	Q9HD89-1
	RETN	NM_001385726.1		c.*62G>A		3_prime_UTR	Exon 4 of 4	NP_001372655.1
	RETN	NM_001193374.2		c.*62G>A		3_prime_UTR	Exon 4 of 4	NP_001180303.1	Q9HD89-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETN	ENST00000221515.6	TSL:1 MANE Select	c.*62G>A		3_prime_UTR	Exon 4 of 4	ENSP00000221515.1	Q9HD89-1
	RETN	ENST00000629642.1	TSL:5	c.*62G>A		3_prime_UTR	Exon 3 of 3	ENSP00000485998.1	Q9HD89-2
	RETN	ENST00000381324.2	TSL:1	c.*62G>A		downstream_gene	N/A	ENSP00000370725.2	Q9HD89-2

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

African (AFR) AF: 0.134 AC: 4131 AN: 30792

American (AMR) AF: 0.0279 AC: 937 AN: 33570

Ashkenazi Jewish (ASJ) AF: 0.00904 AC: 219 AN: 24224

East Asian (EAS) AF: 0.115 AC: 4065 AN: 35332

South Asian (SAS) AF: 0.0386 AC: 2977 AN: 77140

European-Finnish (FIN) AF: 0.0202 AC: 676 AN: 33412

Middle Eastern (MID) AF: 0.0158 AC: 75 AN: 4760

European-Non Finnish (NFE) AF: 0.0359 AC: 38073 AN: 1061180

Other (OTH) AF: 0.0466 AC: 2639 AN: 56628

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

African (AFR) AF: 0.129 AC: 5305 AN: 41124

American (AMR) AF: 0.0468 AC: 696 AN: 14880

Ashkenazi Jewish (ASJ) AF: 0.00812 AC: 28 AN: 3448

East Asian (EAS) AF: 0.154 AC: 767 AN: 4986

South Asian (SAS) AF: 0.0488 AC: 224 AN: 4592

European-Finnish (FIN) AF: 0.0210 AC: 216 AN: 10288

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 290

European-Non Finnish (NFE) AF: 0.0349 AC: 2338 AN: 67064

Other (OTH) AF: 0.0604 AC: 124 AN: 2052

Alfa AF: 0.0479 Hom.: 169

Bravo AF: 0.0694

Asia WGS AF: 0.0840 AC: 294 AN: 3476

ClinVar

ClinVar submissions

Significance: risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Diabetes mellitus type 2, susceptibility to (1)
-	-	-	HYPERTENSION, INSULIN RESISTANCE-RELATED, SUSCEPTIBILITY TO (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.90
PhyloP100		-0.91
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: rs3745368; hg19: chr19-7735297;