19-7670203-G-C

Position:

• chr19-7670203-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020415.4(RETN):​c.197-16G>C variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RETN	NM_020415.4	c.197-16G>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000221515.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RETN	ENST00000221515.6	c.197-16G>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_020415.4	P1
RETN	ENST00000381324.2	c.119-16G>C		splice_polypyrimidine_tract_variant, intron_variant		1
RETN	ENST00000629642.1	c.119-16G>C		splice_polypyrimidine_tract_variant, intron_variant		5

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

GnomAD3 exomes AF: 0.818 AC: 178057 AN: 217660 Hom.: 73490 AF XY: 0.816 AC XY: 98640 AN XY: 120822

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 SAS exome AF: 0.808

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

Gnomad4 AFR exome AF: 0.665

Gnomad4 AMR exome AF: 0.921

Gnomad4 ASJ exome AF: 0.857

Gnomad4 EAS exome AF: 0.697

Gnomad4 SAS exome AF: 0.808

Gnomad4 FIN exome AF: 0.818

Gnomad4 NFE exome AF: 0.831

Gnomad4 OTH exome AF: 0.819

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

Gnomad4 AFR AF: 0.672

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.873

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.811

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.51
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

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