19-7670203-G-C

Variant names:

• chr19-7670203-G-C
• rs10402265
• NM_020415.4:c.197-16G>C

Variant summary

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

The NM_020415.4(RETN):​c.197-16G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 1,591,564 control chromosomes in the GnomAD database, including 538,155 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 0.79 (47085 hom., cov: 23)
  • Exomes 𝑓: 0.82 (491070 hom.)
• Consequence: RETN NM_020415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 11 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.867 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.197-16G>C		intron	N/A	NP_065148.1
	RETN	NM_001385726.1		c.223G>C	p.Val75Leu	missense	Exon 4 of 4	NP_001372655.1
	RETN	NM_001193374.2		c.197-16G>C		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.197-16G>C		intron	N/A	ENSP00000221515.1
	RETN	ENST00000381324.2	TSL:1	c.119-16G>C		intron	N/A	ENSP00000370725.2
	RETN	ENST00000629642.1	TSL:5	c.119-16G>C		intron	N/A	ENSP00000485998.1

Frequencies

GnomAD3 genomes AF: 0.789 AC: 118016 AN: 149622 Hom.: 47059 Cov.: 23

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.809

GnomAD2 exomes AF: 0.818 AC: 178057 AN: 217660 AF XY: 0.816

Gnomad AFR exome AF: 0.662

Gnomad AMR exome AF: 0.924

Gnomad ASJ exome AF: 0.849

Gnomad EAS exome AF: 0.642

Gnomad FIN exome AF: 0.808

Gnomad NFE exome AF: 0.834

Gnomad OTH exome AF: 0.839

GnomAD4 exome AF: 0.824 AC: 1188584 AN: 1441832 Hom.: 491070 Cov.: 40 AF XY: 0.824 AC XY: 591202 AN XY: 717136

African (AFR) AF: 0.665 AC: 22151 AN: 33298

American (AMR) AF: 0.921 AC: 40404 AN: 43858

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 22180 AN: 25894

East Asian (EAS) AF: 0.697 AC: 27396 AN: 39318

South Asian (SAS) AF: 0.808 AC: 68680 AN: 85010

European-Finnish (FIN) AF: 0.818 AC: 34298 AN: 41918

Middle Eastern (MID) AF: 0.889 AC: 4618 AN: 5196

European-Non Finnish (NFE) AF: 0.831 AC: 919918 AN: 1107558

Other (OTH) AF: 0.819 AC: 48939 AN: 59782

GnomAD4 genome AF: 0.789 AC: 118091 AN: 149732 Hom.: 47085 Cov.: 23 AF XY: 0.789 AC XY: 57655 AN XY: 73034

African (AFR) AF: 0.672 AC: 27270 AN: 40562

American (AMR) AF: 0.880 AC: 13318 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3021 AN: 3462

East Asian (EAS) AF: 0.653 AC: 3211 AN: 4920

South Asian (SAS) AF: 0.818 AC: 3832 AN: 4682

European-Finnish (FIN) AF: 0.817 AC: 8298 AN: 10154

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56397 AN: 67560

Other (OTH) AF: 0.811 AC: 1677 AN: 2068

Alfa AF: 0.818 Hom.: 9002

Bravo AF: 0.787

Asia WGS AF: 0.767 AC: 2660 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.51
DANN	Benign	0.48
PhyloP100		-2.1
Mutation Taster		=25/75	disease causing

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: rs10402265; hg19: chr19-7735089; COSMIC: COSV55568642; COSMIC: COSV55568642;