chr19-7670589-G-C

Variant names:

• chr19-7670589-G-C
• rs3745369
• NM_020415.4:c.*240G>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.*240G>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 589,572 control chromosomes in the GnomAD database, including 66,348 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 0.46 (16089 hom., cov: 30)
  • Exomes 𝑓: 0.47 (50259 hom.)
• Consequence: RETN NM_020415.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.930
• Publications: 20 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 (SAS) allele frequency at 95% confidence interval = 0.502 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.*240G>C		downstream_gene	N/A	NP_065148.1
	RETN	NM_001385726.1		c.*240G>C		downstream_gene	N/A	NP_001372655.1
	RETN	NM_001193374.2		c.*240G>C		downstream_gene	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.*240G>C		downstream_gene	N/A	ENSP00000221515.1
	RETN	ENST00000381324.2	TSL:1	c.*240G>C		downstream_gene	N/A	ENSP00000370725.2
	RETN	ENST00000629642.1	TSL:5	c.*240G>C		downstream_gene	N/A	ENSP00000485998.1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69390 AN: 151786 Hom.: 16068 Cov.: 30

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.474

GnomAD4 exome AF: 0.474 AC: 207412 AN: 437668 Hom.: 50259 AF XY: 0.477 AC XY: 108897 AN XY: 228454

African (AFR) AF: 0.389 AC: 4677 AN: 12010

American (AMR) AF: 0.519 AC: 8986 AN: 17330

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 6933 AN: 13252

East Asian (EAS) AF: 0.297 AC: 8770 AN: 29524

South Asian (SAS) AF: 0.531 AC: 21790 AN: 41032

European-Finnish (FIN) AF: 0.422 AC: 12209 AN: 28914

Middle Eastern (MID) AF: 0.492 AC: 930 AN: 1890

European-Non Finnish (NFE) AF: 0.488 AC: 131046 AN: 268520

Other (OTH) AF: 0.479 AC: 12071 AN: 25196

GnomAD4 genome AF: 0.457 AC: 69464 AN: 151904 Hom.: 16089 Cov.: 30 AF XY: 0.456 AC XY: 33862 AN XY: 74216

African (AFR) AF: 0.400 AC: 16581 AN: 41422

American (AMR) AF: 0.512 AC: 7819 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1817 AN: 3470

East Asian (EAS) AF: 0.324 AC: 1661 AN: 5128

South Asian (SAS) AF: 0.519 AC: 2498 AN: 4810

European-Finnish (FIN) AF: 0.412 AC: 4356 AN: 10560

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32957 AN: 67924

Other (OTH) AF: 0.477 AC: 1007 AN: 2112

Alfa AF: 0.464 Hom.: 2010

Bravo AF: 0.461

Asia WGS AF: 0.422 AC: 1471 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	0.76
DANN	Benign	0.60
PhyloP100		-0.93

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3745369; hg19: chr19-7735475;