Genetic Variant RARRES2:p.Arg3Gln (chr7-150340602-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_002889.4(RARRES2):c.8G>A(p.Arg3Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000059 in 1,524,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

RARRES2
NM_002889.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.90

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02984479).

BP6

Variant 7-150340602-C-T is Benign according to our data. Variant chr7-150340602-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2257913.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002889.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARRES2	NM_002889.4	MANE Select	c.8G>A	p.Arg3Gln	missense	Exon 2 of 6	NP_002880.1	A0A090N7U9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RARRES2	ENST00000223271.8	TSL:1 MANE Select	c.8G>A	p.Arg3Gln	missense	Exon 2 of 6	ENSP00000223271.3	Q99969
RARRES2	ENST00000482669.1	TSL:1	c.8G>A	p.Arg3Gln	missense	Exon 2 of 5	ENSP00000418483.1	Q99969
RARRES2	ENST00000466675.5	TSL:2	c.8G>A	p.Arg3Gln	missense	Exon 1 of 5	ENSP00000418009.1	Q99969

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000731

AC:

AN:

136854

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000189

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1372054

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

673356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31252

American (AMR)

AF:

0.00

AC:

AN:

34606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24138

East Asian (EAS)

AF:

0.00

AC:

AN:

35822

South Asian (SAS)

AF:

0.0000128

AC:

AN:

78296

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5156

European-Non Finnish (NFE)

AF:

0.00000376

AC:

AN:

1064682

Other (OTH)

AF:

0.00

AC:

AN:

56742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.0000263

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000483

AC:

AN:

41438

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000164189), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.362

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.94

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.013

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0091

LIST_S2

Benign

0.51

M_CAP

Benign

0.0025

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.23

PhyloP100

-2.9

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.030

REVEL

Benign

0.012

Sift

Benign

0.32

Sift4G

Benign

0.55

Polyphen

0.0030

Vest4

0.074

MutPred

0.24

Loss of MoRF binding (P = 0.0039)

MVP

0.014

MPC

0.13

ClinPred

0.064

GERP RS

-9.4

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.031

gMVP

0.15

Mutation Taster

=95/5

polymorphism

(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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over