dbSNP rs1862513: RETN:c.-225C>G (chr19-7668907-C-G) – 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.-225C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 196,100 control chromosomes in the GnomAD database, including 10,741 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 ( 8729 hom., cov: 31)

Exomes 𝑓: 0.27 ( 2012 hom. )

Consequence

RETN
NM_020415.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.137

Publications

200 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RETN	NM_020415.4 link	c.-225C>G		upstream_gene_variant		ENST00000221515.6	NP_065148.1	Q9HD89-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RETN	ENST00000221515.6 link	c.-225C>G		upstream_gene_variant		1	NM_020415.4	ENSP00000221515.1		Q9HD89-1
RETN	ENST00000629642.1 link	c.-225C>G		upstream_gene_variant		5		ENSP00000485998.1		Q9HD89-2

Frequencies

GnomAD3 genomes

AF:

0.332

AC:

50339

AN:

151838

Hom.:

8723

Cov.:

show subpopulations

Gnomad AFR

AF:

0.429

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.365

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.263

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.333

GnomAD4 exome

AF:

0.272

AC:

12020

AN:

44144

Hom.:

2012

AF XY:

0.281

AC XY:

6626

AN XY:

23598

show subpopulations

African (AFR)

AF:

0.386

AC:

509

AN:

1318

American (AMR)

AF:

0.184

AC:

676

AN:

3666

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

274

AN:

966

East Asian (EAS)

AF:

0.307

AC:

854

AN:

2780

South Asian (SAS)

AF:

0.383

AC:

1993

AN:

5210

European-Finnish (FIN)

AF:

0.210

AC:

428

AN:

2042

Middle Eastern (MID)

AF:

0.354

AC:

AN:

144

European-Non Finnish (NFE)

AF:

0.258

AC:

6626

AN:

25714

Other (OTH)

AF:

0.264

AC:

609

AN:

2304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

391

782

1172

1563

1954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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:

0.331

AC:

50373

AN:

151956

Hom.:

8729

Cov.:

AF XY:

0.329

AC XY:

24431

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.429

AC:

17768

AN:

41430

American (AMR)

AF:

0.233

AC:

3559

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.311

AC:

1079

AN:

3470

East Asian (EAS)

AF:

0.365

AC:

1873

AN:

5132

South Asian (SAS)

AF:

0.410

AC:

1976

AN:

4820

European-Finnish (FIN)

AF:

0.263

AC:

2774

AN:

10558

Middle Eastern (MID)

AF:

0.414

AC:

121

AN:

292

European-Non Finnish (NFE)

AF:

0.300

AC:

20390

AN:

67946

Other (OTH)

AF:

0.330

AC:

698

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1684

3368

5052

6736

8420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<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:

0.167

Hom.:

302

Bravo

AF:

0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.3

(source)

DANN

Benign

0.55

PhyloP100

-0.14

PromoterAI

0.0046

Neutral

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over