rs1805343

Variant names:

• chr9-134436440-G-A
• rs1805343
• NM_002957.6:c.1242-27G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-134436440-G-A
• chr9-134436440-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002957.6(RXRA):​c.1242-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 1,610,376 control chromosomes in the GnomAD database, including 320,972 homozygotes. 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: 𝑓 0.53 (23813 hom., cov: 35)
  • Exomes 𝑓: 0.63 (297159 hom.)
• Consequence: RXRA NM_002957.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85
• Publications: 35 publications found

Genes affected

RXRA (HGNC:10477): (retinoid X receptor alpha) Retinoid X receptors (RXRs) and retinoic acid receptors (RARs) are nuclear receptors that mediate the biological effects of retinoids by their involvement in retinoic acid-mediated gene activation. These receptors function as transcription factors by binding as homodimers or heterodimers to specific sequences in the promoters of target genes. The protein encoded by this gene is a member of the steroid and thyroid hormone receptor superfamily of transcriptional regulators. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXRA	NM_002957.6	c.1242-27G>A		intron_variant	Intron 9 of 9	ENST00000481739.2	NP_002948.1
RXRA	NM_001291920.2	c.1161-27G>A		intron_variant	Intron 9 of 9		NP_001278849.1
RXRA	NM_001291921.2	c.951-27G>A		intron_variant	Intron 8 of 8		NP_001278850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXRA	ENST00000481739.2	c.1242-27G>A		intron_variant	Intron 9 of 9	1	NM_002957.6	ENSP00000419692.1
RXRA	ENST00000672570.1	c.1161-27G>A		intron_variant	Intron 9 of 9			ENSP00000500402.1
RXRA	ENST00000356384.4	n.1652-27G>A		intron_variant	Intron 11 of 11	5

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80778 AN: 152088 Hom.: 23816 Cov.: 35

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.562

GnomAD2 exomes AF: 0.593 AC: 147282 AN: 248256 AF XY: 0.595

Gnomad AFR exome AF: 0.251

Gnomad AMR exome AF: 0.580

Gnomad ASJ exome AF: 0.664

Gnomad EAS exome AF: 0.648

Gnomad FIN exome AF: 0.647

Gnomad NFE exome AF: 0.650

Gnomad OTH exome AF: 0.606

GnomAD4 exome AF: 0.634 AC: 924124 AN: 1458168 Hom.: 297159 Cov.: 39 AF XY: 0.630 AC XY: 457062 AN XY: 725518

African (AFR) AF: 0.250 AC: 8368 AN: 33432

American (AMR) AF: 0.577 AC: 25715 AN: 44600

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 17314 AN: 25990

East Asian (EAS) AF: 0.658 AC: 26106 AN: 39690

South Asian (SAS) AF: 0.486 AC: 41793 AN: 86060

European-Finnish (FIN) AF: 0.648 AC: 33761 AN: 52086

Middle Eastern (MID) AF: 0.576 AC: 3318 AN: 5758

European-Non Finnish (NFE) AF: 0.658 AC: 730603 AN: 1110274

Other (OTH) AF: 0.616 AC: 37146 AN: 60278

GnomAD4 genome AF: 0.531 AC: 80776 AN: 152208 Hom.: 23813 Cov.: 35 AF XY: 0.533 AC XY: 39676 AN XY: 74412

African (AFR) AF: 0.259 AC: 10755 AN: 41512

American (AMR) AF: 0.574 AC: 8780 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2208 AN: 3470

East Asian (EAS) AF: 0.658 AC: 3409 AN: 5180

South Asian (SAS) AF: 0.489 AC: 2360 AN: 4824

European-Finnish (FIN) AF: 0.642 AC: 6811 AN: 10608

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44521 AN: 68002

Other (OTH) AF: 0.556 AC: 1176 AN: 2114

Alfa AF: 0.605 Hom.: 84263

Bravo AF: 0.516

Asia WGS AF: 0.560 AC: 1951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.051
DANN	Benign	0.62
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1805343; hg19: chr9-137328286; COSMIC: COSV62683543;