NM_020415.4:c.197-154C>G

Variant names:

• chr19-7670065-C-G
• rs3219178
• NM_020415.4:c.197-154C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020415.4(RETN):​c.197-154C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 149,708 control chromosomes in the GnomAD database, including 9,931 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 0.33 (9931 hom., cov: 25)
• Consequence: RETN NM_020415.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RETN	NM_020415.4	c.197-154C>G		intron_variant	Intron 3 of 3	ENST00000221515.6	NP_065148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RETN	ENST00000221515.6	c.197-154C>G		intron_variant	Intron 3 of 3	1	NM_020415.4	ENSP00000221515.1
RETN	ENST00000381324.2	c.119-154C>G		intron_variant	Intron 1 of 1	1		ENSP00000370725.2
RETN	ENST00000629642.1	c.119-154C>G		intron_variant	Intron 2 of 2	5		ENSP00000485998.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 48933 AN: 149592 Hom.: 9927 Cov.: 25

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.317

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.327 AC: 48947 AN: 149708 Hom.: 9931 Cov.: 25 AF XY: 0.325 AC XY: 23607 AN XY: 72738

African (AFR) AF: 0.0877 AC: 3610 AN: 41166

American (AMR) AF: 0.316 AC: 4751 AN: 15020

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1431 AN: 3452

East Asian (EAS) AF: 0.258 AC: 1290 AN: 4994

South Asian (SAS) AF: 0.396 AC: 1851 AN: 4674

European-Finnish (FIN) AF: 0.478 AC: 4712 AN: 9866

Middle Eastern (MID) AF: 0.290 AC: 84 AN: 290

European-Non Finnish (NFE) AF: 0.447 AC: 30055 AN: 67292

Other (OTH) AF: 0.318 AC: 656 AN: 2062

Alfa AF: 0.382 Hom.: 1528

Bravo AF: 0.309

Asia WGS AF: 0.355 AC: 1231 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.48
PhyloP100		0.11
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: rs3219178; hg19: chr19-7734951;