rs201059237

Variant names:

• chr6-33196472-C-T
• rs201059237
• NM_021976.5:c.955G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_021976.5(RXRB):​c.955G>A​(p.Val319Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,613,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: RXRB NM_021976.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.537
• Publications: 2 publications found

Genes affected

RXRB (HGNC:10478): (retinoid X receptor beta) This gene encodes a member of the retinoid X receptor (RXR) family of nuclear receptors which are involved in mediating the effects of retinoic acid (RA). The encoded protein forms homodimers with the retinoic acid, thyroid hormone, and vitamin D receptors, increasing both DNA binding and transcriptional function on their respective response elements. This gene lies within the major histocompatibility complex (MHC) class II region on chromosome 6. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023199797).
• BP6: Variant 6-33196472-C-T is Benign according to our data. Variant chr6-33196472-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2522153.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 30 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021976.5. 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
	RXRB	NM_021976.5	MANE Select	c.955G>A	p.Val319Ile	missense	Exon 5 of 10	NP_068811.1	Q5STP9
	RXRB	NM_001270401.2		c.955G>A	p.Val319Ile	missense	Exon 5 of 10	NP_001257330.1	A0A0S2Z570
	RXRB	NM_001291989.2		c.385G>A	p.Val129Ile	missense	Exon 4 of 9	NP_001278918.1	A0A0G2JKR7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRB	ENST00000374680.4	TSL:1 MANE Select	c.955G>A	p.Val319Ile	missense	Exon 5 of 10	ENSP00000363812.3	P28702-1
	RXRB	ENST00000374685.8	TSL:1	c.955G>A	p.Val319Ile	missense	Exon 5 of 10	ENSP00000363817.4	P28702-3
	RXRB	ENST00000865272.1		c.955G>A	p.Val319Ile	missense	Exon 5 of 10	ENSP00000535331.1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000239 AC: 59 AN: 246464 AF XY: 0.000231

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000551

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000547

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000262

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000141 AC: 206 AN: 1460742 Hom.: 0 Cov.: 32 AF XY: 0.000144 AC XY: 105 AN XY: 726684

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000604 AC: 27 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000325 AC: 28 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52300

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.000101 AC: 112 AN: 1111990

Other (OTH) AF: 0.000331 AC: 20 AN: 60386

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152338 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74484

African (AFR) AF: 0.0000962 AC: 4 AN: 41568

American (AMR) AF: 0.00105 AC: 16 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000189 Hom.: 0

Bravo AF: 0.000162

ExAC AF: 0.000213 AC: 25

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000415

ClinVar

ClinVar submissions as Germline

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	0.072
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.28	N
PhyloP100		0.54
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.11
Sift	Benign	0.38	T
Sift4G	Benign	0.55	T
Polyphen		0.059	B
Vest4		0.087
MVP		0.38
MPC		0.83
ClinPred		0.013	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.027
gMVP		0.062
Mutation Taster		=81/19	polymorphism

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: rs201059237; hg19: chr6-33164249; COSMIC: COSV108877640; COSMIC: COSV108877640;