6-33194451-A-G

Variant names:

• chr6-33194451-A-G
• rs5030979
• NM_021976.5:c.*231T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021976.5(RXRB):​c.*231T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RXRB NM_021976.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 7 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).

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.*231T>C		3_prime_UTR	Exon 10 of 10	NP_068811.1
	RXRB	NM_001270401.2		c.*231T>C		3_prime_UTR	Exon 10 of 10	NP_001257330.1
	RXRB	NM_001291989.2		c.*231T>C		3_prime_UTR	Exon 9 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.*231T>C		3_prime_UTR	Exon 10 of 10	ENSP00000363812.3
	RXRB	ENST00000374685.8	TSL:1	c.*231T>C		3_prime_UTR	Exon 10 of 10	ENSP00000363817.4
	RXRB	ENST00000483281.5	TSL:5	n.*1345T>C		non_coding_transcript_exon	Exon 9 of 9	ENSP00000431369.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 354790 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 183618

African (AFR) AF: 0.00 AC: 0 AN: 10302

American (AMR) AF: 0.00 AC: 0 AN: 12720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11638

East Asian (EAS) AF: 0.00 AC: 0 AN: 26804

South Asian (SAS) AF: 0.00 AC: 0 AN: 24026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 220392

Other (OTH) AF: 0.00 AC: 0 AN: 21838

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	10
DANN	Benign	0.71
PhyloP100		0.14

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: rs5030979; hg19: chr6-33162228;