NM_206963.2:c.277A>G

Variant names:

• chr3-158713859-T-C
• rs201288879
• NM_206963.2:c.277A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_206963.2(RARRES1):​c.277A>G​(p.Ile93Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,613,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: RARRES1 NM_206963.2 missense, splice_region
• Scores: Splicing: ADA: 0.00001299
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.329
• Publications: 0 publications found

Genes affected

RARRES1 (HGNC:9867): (retinoic acid receptor responder 1) This gene was identified as a retinoid acid (RA) receptor-responsive gene. It encodes a type 1 membrane protein. The expression of this gene is upregulated by tazarotene as well as by retinoic acid receptors. The expression of this gene is found to be downregulated in prostate cancer, which is caused by the methylation of its promoter and CpG island. Alternatively spliced transcript variant encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04669726).
• BP6: Variant 3-158713859-T-C is Benign according to our data. Variant chr3-158713859-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3786943.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206963.2. 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
	RARRES1	NM_206963.2	MANE Select	c.277A>G	p.Ile93Val	missense splice_region	Exon 2 of 6	NP_996846.1	P49788-1
	RARRES1	NM_002888.4		c.277A>G	p.Ile93Val	missense splice_region	Exon 2 of 4	NP_002879.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARRES1	ENST00000237696.10	TSL:1 MANE Select	c.277A>G	p.Ile93Val	missense splice_region	Exon 2 of 6	ENSP00000237696.5	P49788-1
	RARRES1	ENST00000479756.1	TSL:1	c.277A>G	p.Ile93Val	missense splice_region	Exon 2 of 4	ENSP00000418556.1	P49788-2
	RARRES1	ENST00000879325.1		c.277A>G	p.Ile93Val	missense splice_region	Exon 2 of 6	ENSP00000549384.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152204 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250418 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000452 AC: 66 AN: 1460862 Hom.: 0 Cov.: 30 AF XY: 0.0000440 AC XY: 32 AN XY: 726842

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000549 AC: 61 AN: 1111122

Other (OTH) AF: 0.0000663 AC: 4 AN: 60354

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152204 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000494 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.37
DANN	Benign	0.25
DEOGEN2	Benign	0.00080	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.23	N
PhyloP100		-0.33
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.035
Sift	Benign	1.0	T
Sift4G	Benign	0.70	T
Polyphen		0.0010	B
Vest4		0.088
MutPred		0.33		Loss of methylation at K96 (P = 0.1065)
MVP		0.17
MPC		0.37
ClinPred		0.022	T
GERP RS		-1.9
Varity_R		0.021
gMVP		0.080
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000013
dbscSNV1_RF	Benign	0.0020
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: rs201288879; hg19: chr3-158431648;