Genetic Variant RETN:c.197-16G>C (chr19-7670203-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001385726.1(RETN):c.223G>C(p.Val75Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 1,591,564 control chromosomes in the GnomAD database, including 538,155 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.79 ( 47085 hom., cov: 23)

Exomes 𝑓: 0.82 ( 491070 hom. )

Consequence

RETN
NM_001385726.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.07

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 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=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RETN	NM_020415.4 link	c.197-16G>C		intron_variant	Intron 3 of 3	ENST00000221515.6	NP_065148.1	Q9HD89-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RETN	ENST00000221515.6 link	c.197-16G>C	intron_variant	Intron 3 of 3	1	NM_020415.4	ENSP00000221515.1	Q9HD89-1
RETN	ENST00000381324.2 link	c.119-16G>C	intron_variant	Intron 1 of 1	1		ENSP00000370725.2	Q9HD89-2
RETN	ENST00000629642.1 link	c.119-16G>C	intron_variant	Intron 2 of 2	5		ENSP00000485998.1	Q9HD89-2

Frequencies

GnomAD3 genomes

AF:

0.789

AC:

118016

AN:

149622

Hom.:

47059

Cov.:

show subpopulations

Gnomad AFR

AF:

0.673

Gnomad AMI

AF:

0.909

Gnomad AMR

AF:

0.879

Gnomad ASJ

AF:

0.873

Gnomad EAS

AF:

0.652

Gnomad SAS

AF:

0.818

Gnomad FIN

AF:

0.817

Gnomad MID

AF:

0.873

Gnomad NFE

AF:

0.835

Gnomad OTH

AF:

0.809

GnomAD2 exomes

AF:

0.818

AC:

178057

AN:

217660

AF XY:

0.816

show subpopulations

Gnomad AFR exome

AF:

0.662

Gnomad AMR exome

AF:

0.924

Gnomad ASJ exome

AF:

0.849

Gnomad EAS exome

AF:

0.642

Gnomad FIN exome

AF:

0.808

Gnomad NFE exome

AF:

0.834

Gnomad OTH exome

AF:

0.839

GnomAD4 exome

AF:

0.824

AC:

1188584

AN:

1441832

Hom.:

491070

Cov.:

AF XY:

0.824

AC XY:

591202

AN XY:

717136

show subpopulations

Gnomad4 AFR exome

AF:

0.665

AC:

22151

AN:

33298

Gnomad4 AMR exome

AF:

0.921

AC:

40404

AN:

43858

Gnomad4 ASJ exome

AF:

0.857

AC:

22180

AN:

25894

Gnomad4 EAS exome

AF:

0.697

AC:

27396

AN:

39318

Gnomad4 SAS exome

AF:

0.808

AC:

68680

AN:

85010

Gnomad4 FIN exome

AF:

0.818

AC:

34298

AN:

41918

Gnomad4 NFE exome

AF:

0.831

AC:

919918

AN:

1107558

Gnomad4 Remaining exome

AF:

0.819

AC:

48939

AN:

59782

Heterozygous variant carriers

9780

19560

29341

39121

48901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

20938

41876

62814

83752

104690

<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:

0.789

AC:

118091

AN:

149732

Hom.:

47085

Cov.:

AF XY:

0.789

AC XY:

57655

AN XY:

73034

show subpopulations

Gnomad4 AFR

AF:

0.672

AC:

0.672304

AN:

0.672304

Gnomad4 AMR

AF:

0.880

AC:

0.879773

AN:

0.879773

Gnomad4 ASJ

AF:

0.873

AC:

0.872617

AN:

0.872617

Gnomad4 EAS

AF:

0.653

AC:

0.652642

AN:

0.652642

Gnomad4 SAS

AF:

0.818

AC:

0.818454

AN:

0.818454

Gnomad4 FIN

AF:

0.817

AC:

0.817215

AN:

0.817215

Gnomad4 NFE

AF:

0.835

AC:

0.834769

AN:

0.834769

Gnomad4 OTH

AF:

0.811

AC:

0.810928

AN:

0.810928

Heterozygous variant carriers

1157

2313

3470

4626

5783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.818

Hom.:

9002

Bravo

AF:

0.787

Asia WGS

AF:

0.767

AC:

2660

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.51

DANN

Benign

0.48

Mutation Taster

=25/75

disease causing

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over