dbSNP rs3219175: RETN:c.-163G>A (chr19-7668969-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020415.4(RETN):c.-163G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 297,674 control chromosomes in the GnomAD database, including 684 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 0.050 ( 512 hom., cov: 31)

Exomes 𝑓: 0.021 ( 172 hom. )

Consequence

RETN
NM_020415.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.61

Publications

50 publications found

Variant links:

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

RETN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.178 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RETN	NM_020415.4	MANE Select	c.-163G>A	upstream_gene	N/A	NP_065148.1	Q9HD89-1
RETN	NM_001385726.1		c.-163G>A	upstream_gene	N/A	NP_001372655.1
RETN	NM_001193374.2		c.-154G>A	upstream_gene	N/A	NP_001180303.1	Q9HD89-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RETN	ENST00000221515.6	TSL:1 MANE Select	c.-163G>A		upstream_gene	N/A	ENSP00000221515.1	Q9HD89-1
	RETN	ENST00000629642.1	TSL:5	c.-163G>A		upstream_gene	N/A	ENSP00000485998.1	Q9HD89-2

Frequencies

GnomAD3 genomes

AF:

0.0503

AC:

7639

AN:

151994

Hom.:

511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0155

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.0280

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00847

Gnomad OTH

AF:

0.0311

GnomAD4 exome

AF:

0.0211

AC:

3078

AN:

145562

Hom.:

172

AF XY:

0.0207

AC XY:

1598

AN XY:

77198

show subpopulations

African (AFR)

AF:

0.123

AC:

574

AN:

4660

American (AMR)

AF:

0.0103

AC:

AN:

5940

Ashkenazi Jewish (ASJ)

AF:

0.00129

AC:

AN:

3886

East Asian (EAS)

AF:

0.176

AC:

1273

AN:

7218

South Asian (SAS)

AF:

0.0197

AC:

408

AN:

20758

European-Finnish (FIN)

AF:

0.00253

AC:

AN:

7898

Middle Eastern (MID)

AF:

0.00871

AC:

AN:

574

European-Non Finnish (NFE)

AF:

0.00672

AC:

584

AN:

86946

Other (OTH)

AF:

0.0193

AC:

148

AN:

7682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

138

277

415

554

692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0503

AC:

7653

AN:

152112

Hom.:

512

Cov.:

AF XY:

0.0493

AC XY:

3668

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.136

AC:

5628

AN:

41472

American (AMR)

AF:

0.0154

AC:

236

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.188

AC:

967

AN:

5142

South Asian (SAS)

AF:

0.0278

AC:

134

AN:

4822

European-Finnish (FIN)

AF:

0.00377

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00846

AC:

575

AN:

67992

Other (OTH)

AF:

0.0313

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

321

642

962

1283

1604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0198

Hom.:

130

Bravo

AF:

0.0562

Asia WGS

AF:

0.100

AC:

346

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

1.6

PromoterAI

0.27

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over