19-7670411-G-T

Variant names:

• chr19-7670411-G-T
• rs3745368
• NM_020415.4:c.*62G>T

Variant summary

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

The NM_020415.4(RETN):​c.*62G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,357,238 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: RETN NM_020415.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.905
• 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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RETN	NM_020415.4	c.*62G>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000221515.6	NP_065148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RETN	ENST00000221515.6	c.*62G>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_020415.4	ENSP00000221515.1
RETN	ENST00000629642.1	c.*62G>T		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000485998.1
RETN	ENST00000381324.2	c.*62G>T		downstream_gene_variant		1		ENSP00000370725.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1357238 Hom.: 0 Cov.: 30 AF XY: 0.00000150 AC XY: 1 AN XY: 667914

African (AFR) AF: 0.00 AC: 0 AN: 30816

American (AMR) AF: 0.00 AC: 0 AN: 33576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24224

East Asian (EAS) AF: 0.00 AC: 0 AN: 35340

South Asian (SAS) AF: 0.00 AC: 0 AN: 77150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4760

European-Non Finnish (NFE) AF: 9.42e-7 AC: 1 AN: 1061324

Other (OTH) AF: 0.00 AC: 0 AN: 56632

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.83
PhyloP100		-0.91

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;