rs61730281

Variant names:

• chr6-33198324-G-A
• rs61730281
• NM_021976.5:c.624C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_021976.5(RXRB):​c.624C>T​(p.Cys208Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,613,012 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0016 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (76 hom.)
• Consequence: RXRB NM_021976.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.82
• Publications: 1 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 -9 ACMG points.

• BP6: Variant 6-33198324-G-A is Benign according to our data. Variant chr6-33198324-G-A is described in ClinVar as Benign. ClinVar VariationId is 3042895.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00156 (237/152292) while in subpopulation SAS AF = 0.0333 (161/4828). AF 95% confidence interval is 0.0291. There are 5 homozygotes in GnomAd4. There are 155 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 237 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.624C>T	p.Cys208Cys	synonymous	Exon 3 of 10	NP_068811.1	Q5STP9
	RXRB	NM_001270401.2		c.624C>T	p.Cys208Cys	synonymous	Exon 3 of 10	NP_001257330.1	A0A0S2Z570
	RXRB	NM_001291989.2		c.54C>T	p.Cys18Cys	synonymous	Exon 2 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.624C>T	p.Cys208Cys	synonymous	Exon 3 of 10	ENSP00000363812.3	P28702-1
	RXRB	ENST00000374685.8	TSL:1	c.624C>T	p.Cys208Cys	synonymous	Exon 3 of 10	ENSP00000363817.4	P28702-3
	RXRB	ENST00000865272.1		c.624C>T	p.Cys208Cys	synonymous	Exon 3 of 10	ENSP00000535331.1

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 235 AN: 152174 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0329

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00438 AC: 1077 AN: 245712 AF XY: 0.00589

Gnomad AFR exome AF: 0.000995

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00181

Gnomad EAS exome AF: 0.00241

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000173

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00223 AC: 3254 AN: 1460720 Hom.: 76 Cov.: 32 AF XY: 0.00318 AC XY: 2312 AN XY: 726682

African (AFR) AF: 0.000657 AC: 22 AN: 33476

American (AMR) AF: 0.0000671 AC: 3 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 31 AN: 26134

East Asian (EAS) AF: 0.00154 AC: 61 AN: 39700

South Asian (SAS) AF: 0.0325 AC: 2806 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52304

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.000114 AC: 127 AN: 1111982

Other (OTH) AF: 0.00325 AC: 196 AN: 60380

GnomAD4 genome AF: 0.00156 AC: 237 AN: 152292 Hom.: 5 Cov.: 32 AF XY: 0.00208 AC XY: 155 AN XY: 74464

African (AFR) AF: 0.000866 AC: 36 AN: 41554

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5182

South Asian (SAS) AF: 0.0333 AC: 161 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68026

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000311 Hom.: 0

Bravo AF: 0.000631

Asia WGS AF: 0.0200 AC: 70 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000415

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	RXRB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		1.8
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.21		Position offset: -16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61730281; hg19: chr6-33166101; COSMIC: COSV63399506; COSMIC: COSV63399506;