19-7670203-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001385726.1(RETN):​c.223G>T​(p.Val75Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RETN NM_001385726.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385726.1. 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.197-16G>T		intron	N/A	NP_065148.1	Q9HD89-1
	RETN	NM_001385726.1		c.223G>T	p.Val75Leu	missense	Exon 4 of 4	NP_001372655.1
	RETN	NM_001193374.2		c.197-16G>T		intron	N/A	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.197-16G>T		intron	N/A	ENSP00000221515.1	Q9HD89-1
	RETN	ENST00000381324.2	TSL:1	c.119-16G>T		intron	N/A	ENSP00000370725.2	Q9HD89-2
	RETN	ENST00000629642.1	TSL:5	c.119-16G>T		intron	N/A	ENSP00000485998.1	Q9HD89-2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442488 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 717472

African (AFR) AF: 0.00 AC: 0 AN: 33320

American (AMR) AF: 0.00 AC: 0 AN: 43874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25900

East Asian (EAS) AF: 0.00 AC: 0 AN: 39362

South Asian (SAS) AF: 0.00 AC: 0 AN: 85056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5200

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107972

Other (OTH) AF: 0.00 AC: 0 AN: 59806

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.57
DANN	Benign	0.32
PhyloP100		-2.1

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;