Genetic Variant NM_002889.4:c.*39G>C (chr7-150338411-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_002889.4(RARRES2):c.*39G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 1,512,648 control chromosomes in the GnomAD database, including 53,725 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 0.25 ( 5183 hom., cov: 33)

Exomes 𝑓: 0.26 ( 48542 hom. )

Consequence

RARRES2
NM_002889.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.50

Publications

17 publications found

Variant links:

Genes affected

RARRES2 (HGNC:9868): (retinoic acid receptor responder 2) This gene encodes a secreted chemotactic protein that initiates chemotaxis via the ChemR23 G protein-coupled seven-transmembrane domain ligand. Expression of this gene is upregulated by the synthetic retinoid tazarotene and occurs in a wide variety of tissues. The active protein has several roles, including that as an adipokine and as an antimicrobial protein with activity against bacteria and fungi. [provided by RefSeq, Nov 2014]

RARRES2 links:

ENSG00000301866 (HGNC:):

ENSG00000301866 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 (MetaRNN=4.4593215E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARRES2	NM_002889.4 link	c.*39G>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000223271.8	NP_002880.1
RARRES2	XR_007060121.1 link	n.619G>C		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARRES2	ENST00000223271.8 link	c.*39G>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_002889.4	ENSP00000223271.3

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38747

AN:

151976

Hom.:

5189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.164

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.283

Gnomad SAS

AF:

0.286

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.265

Gnomad OTH

AF:

0.233

GnomAD2 exomes

AF:

0.248

AC:

34053

AN:

137218

AF XY:

0.254

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.283

Gnomad FIN exome

AF:

0.340

Gnomad NFE exome

AF:

0.265

Gnomad OTH exome

AF:

0.238

GnomAD4 exome

AF:

0.264

AC:

359839

AN:

1360554

Hom.:

48542

Cov.:

AF XY:

0.266

AC XY:

178222

AN XY:

671152

show subpopulations

African (AFR)

AF:

0.236

AC:

7324

AN:

31084

American (AMR)

AF:

0.126

AC:

4390

AN:

34924

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

8042

AN:

24462

East Asian (EAS)

AF:

0.342

AC:

11528

AN:

33716

South Asian (SAS)

AF:

0.280

AC:

21915

AN:

78172

European-Finnish (FIN)

AF:

0.344

AC:

10894

AN:

31654

Middle Eastern (MID)

AF:

0.254

AC:

1416

AN:

5576

European-Non Finnish (NFE)

AF:

0.263

AC:

279588

AN:

1064488

Other (OTH)

AF:

0.261

AC:

14742

AN:

56478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

13765

27530

41296

55061

68826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9610

19220

28830

38440

48050

<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:

0.255

AC:

38764

AN:

152094

Hom.:

5183

Cov.:

AF XY:

0.259

AC XY:

19263

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.235

AC:

9765

AN:

41496

American (AMR)

AF:

0.163

AC:

2495

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1096

AN:

3470

East Asian (EAS)

AF:

0.283

AC:

1463

AN:

5170

South Asian (SAS)

AF:

0.285

AC:

1373

AN:

4818

European-Finnish (FIN)

AF:

0.344

AC:

3640

AN:

10580

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.265

AC:

18014

AN:

67964

Other (OTH)

AF:

0.230

AC:

486

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1481

2962

4442

5923

7404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.205

Hom.:

704

Bravo

AF:

0.238

TwinsUK

AF:

0.256

AC:

948

ALSPAC

AF:

0.257

AC:

991

ExAC

AF:

0.245

AC:

5891

Asia WGS

AF:

0.275

AC:

960

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.16

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.036

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.23

MetaRNN

Benign

0.00045

MetaSVM

Benign

-0.99

PhyloP100

-1.5

PROVEAN

Benign

-1.3

REVEL

Benign

0.019

Sift

Uncertain

0.022

ClinPred

0.0046

GERP RS

-5.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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