Genetic Variant RARRES2:c.*39G>A (chr7-150338411-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002889.4(RARRES2):c.*39G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000172 in 1,513,322 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

RARRES2
NM_002889.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.50

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:

ENSG00000261305 (HGNC:):

ENSG00000261305 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06107956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RARRES2	NM_002889.4 link	c.*39G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000223271.8	NP_002880.1	Q99969A0A090N7U9
RARRES2	XR_007060121.1 link	n.619G>A		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RARRES2	ENST00000223271 link	c.*39G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_002889.4	ENSP00000223271.3		Q99969

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000292

AC:

AN:

137218

AF XY:

0.0000403

show subpopulations

Gnomad AFR exome

AF:

0.000153

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000189

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000154

AC:

AN:

1361290

Hom.:

Cov.:

AF XY:

0.0000149

AC XY:

AN XY:

671518

show subpopulations

Gnomad4 AFR exome

AF:

0.000129

AC:

AN:

31096

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

34930

Gnomad4 ASJ exome

AF:

0.0000408

AC:

AN:

24494

Gnomad4 EAS exome

AF:

0.0000592

AC:

AN:

33784

Gnomad4 SAS exome

AF:

0.0000512

AC:

AN:

78190

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

31696

Gnomad4 NFE exome

AF:

0.00000845

AC:

AN:

1065000

Gnomad4 Remaining exome

AF:

0.0000177

AC:

AN:

56514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<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:

0.0000329

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.000121

AC:

0.000120802

AN:

0.000120802

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00

AC:

AN:

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.00

Hom.:

704

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.27

DANN

Benign

0.94

DEOGEN2

Benign

0.0075

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.32

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.36

REVEL

Benign

0.0040

Sift

Benign

0.38

MutPred

0.33

Gain of sheet (P = 0.0344);

MVP

0.014

ClinPred

0.020

GERP RS

-5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

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