19-7669483-C-T

Position:

• chr19-7669483-C-T

Variant summary

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

The NM_020415.4(RETN):​c.118+39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,428,094 control chromosomes in the GnomAD database, including 33,951 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 0.19 (2839 hom., cov: 30)
  • Exomes 𝑓: 0.21 (31112 hom.)
• Consequence: RETN NM_020415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RETN	NM_020415.4	c.118+39C>T		intron_variant		ENST00000221515.6	NP_065148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RETN	ENST00000221515.6	c.118+39C>T		intron_variant		1	NM_020415.4	ENSP00000221515	P1
RETN	ENST00000381324.2	c.118+39C>T		intron_variant		1		ENSP00000370725
RETN	ENST00000629642.1	c.118+39C>T		intron_variant		5		ENSP00000485998

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28422 AN: 151834 Hom.: 2840 Cov.: 30

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.0285

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.205

GnomAD3 exomes AF: 0.198 AC: 49669 AN: 250382 Hom.: 5843 AF XY: 0.212 AC XY: 28704 AN XY: 135394

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.0971

Gnomad ASJ exome AF: 0.305

Gnomad EAS exome AF: 0.0203

Gnomad SAS exome AF: 0.343

Gnomad FIN exome AF: 0.217

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.211

GnomAD4 exome AF: 0.214 AC: 273619 AN: 1276142 Hom.: 31112 Cov.: 19 AF XY: 0.220 AC XY: 141694 AN XY: 644394

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.298

Gnomad4 EAS exome AF: 0.0491

Gnomad4 SAS exome AF: 0.345

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.187 AC: 28430 AN: 151952 Hom.: 2839 Cov.: 30 AF XY: 0.188 AC XY: 13975 AN XY: 74264

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.0281

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.203

Alfa AF: 0.178 Hom.: 799

Bravo AF: 0.177

Asia WGS AF: 0.148 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.4
DANN	Benign	0.75

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: rs3219177; hg19: chr19-7734369;