7-150340550-G-C

Variant names:

• chr7-150340550-G-C
• rs189776236
• NM_002889.4:c.60C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002889.4(RARRES2):​c.60C>G​(p.Ala20Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,575,062 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (70 hom.)
• Consequence: RARRES2 NM_002889.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.08
• Publications: 1 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=-0.86).
• BP6: Variant 7-150340550-G-C is Benign according to our data. Variant chr7-150340550-G-C is described in ClinVar as Benign. ClinVar VariationId is 771419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.07 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00267 (406/152290) while in subpopulation AMR AF = 0.0192 (294/15302). AF 95% confidence interval is 0.0174. There are 7 homozygotes in GnomAd4. There are 215 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

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.60C>G	p.Ala20Ala	synonymous	Exon 2 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.60C>G	p.Ala20Ala	synonymous	Exon 2 of 6	ENSP00000223271.3	Q99969
	RARRES2	ENST00000482669.1	TSL:1	c.60C>G	p.Ala20Ala	synonymous	Exon 2 of 5	ENSP00000418483.1	Q99969
	RARRES2	ENST00000466675.5	TSL:2	c.60C>G	p.Ala20Ala	synonymous	Exon 1 of 5	ENSP00000418009.1	Q99969

Frequencies

GnomAD3 genomes AF: 0.00265 AC: 404 AN: 152172 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00998 AC: 1799 AN: 180342 AF XY: 0.00768

Gnomad AFR exome AF: 0.000997

Gnomad AMR exome AF: 0.0551

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0161

Gnomad FIN exome AF: 0.0000641

Gnomad NFE exome AF: 0.000227

Gnomad OTH exome AF: 0.00459

GnomAD4 exome AF: 0.00206 AC: 2924 AN: 1422772 Hom.: 70 Cov.: 31 AF XY: 0.00188 AC XY: 1323 AN XY: 704696

African (AFR) AF: 0.000398 AC: 13 AN: 32634

American (AMR) AF: 0.0487 AC: 1895 AN: 38898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25398

East Asian (EAS) AF: 0.0203 AC: 765 AN: 37628

South Asian (SAS) AF: 0.000550 AC: 45 AN: 81802

European-Finnish (FIN) AF: 0.0000206 AC: 1 AN: 48502

Middle Eastern (MID) AF: 0.00106 AC: 6 AN: 5644

European-Non Finnish (NFE) AF: 0.0000960 AC: 105 AN: 1093362

Other (OTH) AF: 0.00160 AC: 94 AN: 58904

GnomAD4 genome AF: 0.00267 AC: 406 AN: 152290 Hom.: 7 Cov.: 32 AF XY: 0.00289 AC XY: 215 AN XY: 74450

African (AFR) AF: 0.000433 AC: 18 AN: 41564

American (AMR) AF: 0.0192 AC: 294 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0157 AC: 81 AN: 5170

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.00472

Asia WGS AF: 0.0110 AC: 37 AN: 3478

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	-0.86
CADD	Benign	0.15
DANN	Benign	0.68
PhyloP100		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs189776236; hg19: chr7-150037639; COSMIC: COSV56232194; COSMIC: COSV56232194;