7-150338988-G-T

Variant names:

• chr7-150338988-G-T
• rs1804764
• NM_002889.4:c.373C>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002889.4(RARRES2):​c.373C>A​(p.Arg125Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00555 in 1,602,528 control chromosomes in the GnomAD database, including 371 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (205 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (166 hom.)
• Consequence: RARRES2 NM_002889.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.001769
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.47
• Publications: 7 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-150338988-G-T is Benign according to our data. Variant chr7-150338988-G-T is described in ClinVar as Benign. ClinVar VariationId is 776268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0978 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.373C>A	p.Arg125Arg	splice_region synonymous	Exon 4 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.373C>A	p.Arg125Arg	splice_region synonymous	Exon 4 of 6	ENSP00000223271.3	Q99969
	RARRES2	ENST00000482669.1	TSL:1	c.373C>A	p.Arg125Arg	splice_region synonymous	Exon 4 of 5	ENSP00000418483.1	Q99969
	RARRES2	ENST00000466675.5	TSL:2	c.373C>A	p.Arg125Arg	splice_region synonymous	Exon 3 of 5	ENSP00000418009.1	Q99969

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4373 AN: 152070 Hom.: 205 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0230

GnomAD2 exomes AF: 0.00749 AC: 1883 AN: 251264 AF XY: 0.00516

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.00451

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000431

Gnomad OTH exome AF: 0.00604

GnomAD4 exome AF: 0.00311 AC: 4507 AN: 1450340 Hom.: 166 Cov.: 31 AF XY: 0.00271 AC XY: 1960 AN XY: 722268

African (AFR) AF: 0.103 AC: 3421 AN: 33120

American (AMR) AF: 0.00501 AC: 224 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26072

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39608

South Asian (SAS) AF: 0.000291 AC: 25 AN: 86026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00994 AC: 57 AN: 5734

European-Non Finnish (NFE) AF: 0.000336 AC: 370 AN: 1101638

Other (OTH) AF: 0.00681 AC: 409 AN: 60030

GnomAD4 genome AF: 0.0289 AC: 4394 AN: 152188 Hom.: 205 Cov.: 32 AF XY: 0.0280 AC XY: 2081 AN XY: 74422

African (AFR) AF: 0.100 AC: 4165 AN: 41490

American (AMR) AF: 0.0101 AC: 154 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68008

Other (OTH) AF: 0.0227 AC: 48 AN: 2110

Alfa AF: 0.00824 Hom.: 109

Bravo AF: 0.0325

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000711

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.1
DANN	Benign	0.73
PhyloP100		1.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Mutation Taster		=92/8	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0018
dbscSNV1_RF	Benign	0.096
SpliceAI score (max)		0.030		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: rs1804764; hg19: chr7-150036077;