NM_002889.4:c.*13A>C

Variant names:

• chr7-150338437-T-G
• rs4721
• NM_002889.4:c.*13A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002889.4(RARRES2):​c.*13A>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,526,646 control chromosomes in the GnomAD database, including 134,126 homozygotes. 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: 𝑓 0.47 (17671 hom., cov: 33)
  • Exomes 𝑓: 0.41 (116455 hom.)
• Consequence: RARRES2 NM_002889.4 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 33 publications found

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]

ENSG00000301866 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.086403E-5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

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.*13A>C		splice_region	Exon 6 of 6	NP_002880.1	A0A090N7U9
	RARRES2	NM_002889.4	MANE Select	c.*13A>C		3_prime_UTR	Exon 6 of 6	NP_002880.1	A0A090N7U9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARRES2	ENST00000223271.8	TSL:1 MANE Select	c.*13A>C		splice_region	Exon 6 of 6	ENSP00000223271.3	Q99969
	RARRES2	ENST00000223271.8	TSL:1 MANE Select	c.*13A>C		3_prime_UTR	Exon 6 of 6	ENSP00000223271.3	Q99969
	RARRES2	ENST00000466675.5	TSL:2	c.*13A>C		splice_region	Exon 5 of 5	ENSP00000418009.1	Q99969

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71173 AN: 151852 Hom.: 17646 Cov.: 33

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.437

GnomAD2 exomes AF: 0.419 AC: 57630 AN: 137530 AF XY: 0.426

Gnomad AFR exome AF: 0.634

Gnomad AMR exome AF: 0.276

Gnomad ASJ exome AF: 0.478

Gnomad EAS exome AF: 0.471

Gnomad FIN exome AF: 0.522

Gnomad NFE exome AF: 0.391

Gnomad OTH exome AF: 0.391

GnomAD4 exome AF: 0.407 AC: 558827 AN: 1374676 Hom.: 116455 Cov.: 35 AF XY: 0.410 AC XY: 278012 AN XY: 678316

African (AFR) AF: 0.642 AC: 20150 AN: 31378

American (AMR) AF: 0.277 AC: 9792 AN: 35326

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 11887 AN: 24842

East Asian (EAS) AF: 0.567 AC: 19891 AN: 35076

South Asian (SAS) AF: 0.512 AC: 40092 AN: 78270

European-Finnish (FIN) AF: 0.520 AC: 17563 AN: 33762

Middle Eastern (MID) AF: 0.460 AC: 2595 AN: 5640

European-Non Finnish (NFE) AF: 0.385 AC: 412866 AN: 1073054

Other (OTH) AF: 0.418 AC: 23991 AN: 57328

GnomAD4 genome AF: 0.469 AC: 71244 AN: 151970 Hom.: 17671 Cov.: 33 AF XY: 0.475 AC XY: 35273 AN XY: 74270

African (AFR) AF: 0.627 AC: 26014 AN: 41458

American (AMR) AF: 0.312 AC: 4768 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1673 AN: 3468

East Asian (EAS) AF: 0.478 AC: 2463 AN: 5154

South Asian (SAS) AF: 0.509 AC: 2448 AN: 4814

European-Finnish (FIN) AF: 0.543 AC: 5729 AN: 10550

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26653 AN: 67936

Other (OTH) AF: 0.435 AC: 918 AN: 2110

Alfa AF: 0.419 Hom.: 6830

Bravo AF: 0.457

TwinsUK AF: 0.378 AC: 1402

ALSPAC AF: 0.381 AC: 1469

ExAC AF: 0.401 AC: 9327

Asia WGS AF: 0.479 AC: 1668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.078
DANN	Benign	0.83
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.000021	T
MetaSVM	Benign	-0.95	T
PhyloP100		-1.4
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.013
Sift	Benign	0.72	T
MutPred		0.39		Gain of glycosylation at R126 (P = 0.0736)
ClinPred		0.0058	T
GERP RS		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4721; hg19: chr7-150035526; COSMIC: COSV56231044; COSMIC: COSV56231044;