chr6-33195620-G-A

Variant names:

• chr6-33195620-G-A
• rs184921826
• NM_021976.5:c.1206C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_021976.5(RXRB):​c.1206C>T​(p.His402His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,613,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: RXRB NM_021976.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.24
• Publications: 0 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 (BayesDel_noAF=-0.59).
• BP6: Variant 6-33195620-G-A is Benign according to our data. Variant chr6-33195620-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3049286.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.
• BS2: High AC in GnomAd4 at 28 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.1206C>T	p.His402His	synonymous	Exon 7 of 10	NP_068811.1	Q5STP9
	RXRB	NM_001270401.2		c.1206C>T	p.His402His	synonymous	Exon 7 of 10	NP_001257330.1	A0A0S2Z570
	RXRB	NM_001291989.2		c.636C>T	p.His212His	synonymous	Exon 6 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.1206C>T	p.His402His	synonymous	Exon 7 of 10	ENSP00000363812.3	P28702-1
	RXRB	ENST00000374685.8	TSL:1	c.1206C>T	p.His402His	synonymous	Exon 7 of 10	ENSP00000363817.4	P28702-3
	RXRB	ENST00000865272.1		c.1131C>T	p.His377His	synonymous	Exon 7 of 10	ENSP00000535331.1

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000308 AC: 76 AN: 246528 AF XY: 0.000320

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00372

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000362

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000150 AC: 219 AN: 1460752 Hom.: 0 Cov.: 31 AF XY: 0.000149 AC XY: 108 AN XY: 726688

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00327 AC: 130 AN: 39700

South Asian (SAS) AF: 0.000209 AC: 18 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52296

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

European-Non Finnish (NFE) AF: 0.0000423 AC: 47 AN: 1112004

Other (OTH) AF: 0.000381 AC: 23 AN: 60386

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74488

African (AFR) AF: 0.0000241 AC: 1 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15300

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

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000818 Hom.: 0

Bravo AF: 0.000268

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.59
CADD	Benign	0.77
DANN	Benign	0.87
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs184921826; hg19: chr6-33163397; COSMIC: COSV59499300; COSMIC: COSV59499300;