7-150338437-T-G

Position:

• chr7-150338437-T-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARRES2	NM_002889.4	c.*13A>C		splice_region_variant	6/6	ENST00000223271.8	NP_002880.1
RARRES2	NM_002889.4	c.*13A>C		3_prime_UTR_variant	6/6	ENST00000223271.8	NP_002880.1
RARRES2	XR_007060121.1	n.593A>C		splice_region_variant, non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARRES2	ENST00000223271.8	c.*13A>C		splice_region_variant	6/6	1	NM_002889.4	ENSP00000223271.3
RARRES2	ENST00000223271.8	c.*13A>C		3_prime_UTR_variant	6/6	1	NM_002889.4	ENSP00000223271.3

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

GnomAD3 exomes AF: 0.419 AC: 57630 AN: 137530 Hom.: 12721 AF XY: 0.426 AC XY: 31739 AN XY: 74510

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 SAS exome AF: 0.512

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

Gnomad4 AFR exome AF: 0.642

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.479

Gnomad4 EAS exome AF: 0.567

Gnomad4 SAS exome AF: 0.512

Gnomad4 FIN exome AF: 0.520

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.418

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

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.435

Alfa AF: 0.424 Hom.: 5241

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 v4.3

Name	Calibrated prediction	Score	Prediction
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
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

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

Other links and lift over

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