dbSNP rs4721: RARRES2:c.*13A>T (chr7-150338437-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002889.4(RARRES2):c.*13A>T variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RARRES2
NM_002889.4 splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.39

Publications

33 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11062136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RARRES2	NM_002889.4 link	c.*13A>T	splice_region_variant	Exon 6 of 6	ENST00000223271.8	NP_002880.1
RARRES2	NM_002889.4 link	c.*13A>T	3_prime_UTR_variant	Exon 6 of 6	ENST00000223271.8	NP_002880.1
RARRES2	XR_007060121.1 link	n.593A>T	splice_region_variant, 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.*13A>T		splice_region_variant	Exon 6 of 6	1	NM_002889.4	ENSP00000223271.3
RARRES2	ENST00000223271.8 link	c.*13A>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_002889.4	ENSP00000223271.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.27e-7

AC:

AN:

1375396

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

678644

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

31396

American (AMR)

AF:

0.00

AC:

AN:

35344

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24880

East Asian (EAS)

AF:

0.00

AC:

AN:

35118

South Asian (SAS)

AF:

0.00

AC:

AN:

78282

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33800

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

9.31e-7

AC:

AN:

1073558

Other (OTH)

AF:

0.00

AC:

AN:

57376

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.11

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.029

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.21

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

PhyloP100

-1.4

PROVEAN

Benign

-0.90

REVEL

Benign

0.049

Sift

Benign

0.72

MutPred

0.39

Gain of glycosylation at R126 (P = 0.0736);

MVP

0.040

ClinPred

0.035

GERP RS

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over