19-7669483-C-T

Variant names:

• chr19-7669483-C-T
• rs3219177
• NM_020415.4:c.118+39C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.307 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.118+39C>T		intron	N/A	NP_065148.1
	RETN	NM_001385726.1		c.118+39C>T		intron	N/A	NP_001372655.1
	RETN	NM_001193374.2		c.118+39C>T		intron	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.118+39C>T		intron	N/A	ENSP00000221515.1
	RETN	ENST00000381324.2	TSL:1	c.118+39C>T		intron	N/A	ENSP00000370725.2
	RETN	ENST00000629642.1	TSL:5	c.118+39C>T		intron	N/A	ENSP00000485998.1

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

GnomAD2 exomes AF: 0.198 AC: 49669 AN: 250382 AF XY: 0.212

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 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

African (AFR) AF: 0.161 AC: 4789 AN: 29752

American (AMR) AF: 0.101 AC: 4500 AN: 44468

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 7456 AN: 25048

East Asian (EAS) AF: 0.0491 AC: 1902 AN: 38766

South Asian (SAS) AF: 0.345 AC: 28538 AN: 82718

European-Finnish (FIN) AF: 0.218 AC: 11473 AN: 52700

Middle Eastern (MID) AF: 0.313 AC: 1708 AN: 5450

European-Non Finnish (NFE) AF: 0.214 AC: 201650 AN: 943050

Other (OTH) AF: 0.214 AC: 11603 AN: 54190

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

African (AFR) AF: 0.159 AC: 6591 AN: 41430

American (AMR) AF: 0.138 AC: 2114 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 996 AN: 3472

East Asian (EAS) AF: 0.0281 AC: 145 AN: 5152

South Asian (SAS) AF: 0.320 AC: 1535 AN: 4790

European-Finnish (FIN) AF: 0.223 AC: 2359 AN: 10564

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14052 AN: 67952

Other (OTH) AF: 0.203 AC: 428 AN: 2110

Alfa AF: 0.180 Hom.: 1246

Bravo AF: 0.177

Asia WGS AF: 0.148 AC: 517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.4
DANN	Benign	0.75
PhyloP100		-0.26
PromoterAI		-0.0054	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs3219177; hg19: chr19-7734369;