6-33195674-G-A

Variant names:

• chr6-33195674-G-A
• rs6531
• NM_021976.5:c.1152C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_021976.5(RXRB):​c.1152C>T​(p.Phe384Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 1,612,344 control chromosomes in the GnomAD database, including 444,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (45628 hom., cov: 32)
  • Exomes 𝑓: 0.74 (399087 hom.)
• Consequence: RXRB NM_021976.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 2.99
• Publications: 52 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 6-33195674-G-A is Benign according to our data. Variant chr6-33195674-G-A is described in ClinVar as Benign. ClinVar VariationId is 1254260.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.99 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRB	NM_021976.5	MANE Select	c.1152C>T	p.Phe384Phe	synonymous	Exon 7 of 10	NP_068811.1
	RXRB	NM_001270401.2		c.1152C>T	p.Phe384Phe	synonymous	Exon 7 of 10	NP_001257330.1
	RXRB	NM_001291989.2		c.582C>T	p.Phe194Phe	synonymous	Exon 6 of 9	NP_001278918.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXRB	ENST00000374680.4	TSL:1 MANE Select	c.1152C>T	p.Phe384Phe	synonymous	Exon 7 of 10	ENSP00000363812.3
	RXRB	ENST00000374685.8	TSL:1	c.1152C>T	p.Phe384Phe	synonymous	Exon 7 of 10	ENSP00000363817.4
	RXRB	ENST00000483281.5	TSL:5	n.*664C>T		non_coding_transcript_exon	Exon 6 of 9	ENSP00000431369.1

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117207 AN: 151966 Hom.: 45589 Cov.: 32

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.791

GnomAD2 exomes AF: 0.775 AC: 190210 AN: 245492 AF XY: 0.776

Gnomad AFR exome AF: 0.840

Gnomad AMR exome AF: 0.794

Gnomad ASJ exome AF: 0.810

Gnomad EAS exome AF: 0.974

Gnomad FIN exome AF: 0.699

Gnomad NFE exome AF: 0.715

Gnomad OTH exome AF: 0.774

GnomAD4 exome AF: 0.737 AC: 1075707 AN: 1460260 Hom.: 399087 Cov.: 56 AF XY: 0.740 AC XY: 537907 AN XY: 726424

African (AFR) AF: 0.848 AC: 28383 AN: 33478

American (AMR) AF: 0.797 AC: 35591 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 21159 AN: 26132

East Asian (EAS) AF: 0.981 AC: 38955 AN: 39700

South Asian (SAS) AF: 0.857 AC: 73900 AN: 86246

European-Finnish (FIN) AF: 0.702 AC: 36570 AN: 52130

Middle Eastern (MID) AF: 0.829 AC: 4780 AN: 5768

European-Non Finnish (NFE) AF: 0.711 AC: 790798 AN: 1111762

Other (OTH) AF: 0.755 AC: 45571 AN: 60368

GnomAD4 genome AF: 0.771 AC: 117302 AN: 152084 Hom.: 45628 Cov.: 32 AF XY: 0.772 AC XY: 57400 AN XY: 74322

African (AFR) AF: 0.835 AC: 34632 AN: 41490

American (AMR) AF: 0.784 AC: 11977 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2773 AN: 3468

East Asian (EAS) AF: 0.968 AC: 5010 AN: 5176

South Asian (SAS) AF: 0.871 AC: 4198 AN: 4818

European-Finnish (FIN) AF: 0.708 AC: 7480 AN: 10568

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48765 AN: 67968

Other (OTH) AF: 0.794 AC: 1673 AN: 2108

Alfa AF: 0.744 Hom.: 93182

Bravo AF: 0.781

Asia WGS AF: 0.879 AC: 3057 AN: 3478

EpiCase AF: 0.732

EpiControl AF: 0.739

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

RXRB-related disorder Benign:1

Oct 16, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

not provided Benign:1

Sep 27, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		3.0
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs6531; hg19: chr6-33163451; COSMIC: COSV59500334; COSMIC: COSV59500334;