rs482284

Positions:

• chr17-40347989-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000254066.10(RARA):​c.179-327A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 231,096 control chromosomes in the GnomAD database, including 44,151 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 0.55 (26825 hom., cov: 32)
  • Exomes 𝑓: 0.65 (17326 hom.)
• Consequence: RARA ENST00000254066.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

Genes affected

RARA (HGNC:9864): (retinoic acid receptor alpha) This gene represents a nuclear retinoic acid receptor. The encoded protein, retinoic acid receptor alpha, regulates transcription in a ligand-dependent manner. This gene has been implicated in regulation of development, differentiation, apoptosis, granulopoeisis, and transcription of clock genes. Translocations between this locus and several other loci have been associated with acute promyelocytic leukemia. Alternatively spliced transcript variants have been found for this locus.[provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARA	NM_000964.4	c.179-327A>G		intron_variant		ENST00000254066.10	NP_000955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARA	ENST00000254066.10	c.179-327A>G		intron_variant		1	NM_000964.4	ENSP00000254066	P4

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84154 AN: 151876 Hom.: 26827 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.587

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.603

GnomAD4 exome AF: 0.648 AC: 51226 AN: 79102 Hom.: 17326 AF XY: 0.652 AC XY: 25993 AN XY: 39848

Gnomad4 AFR exome AF: 0.230

Gnomad4 AMR exome AF: 0.700

Gnomad4 ASJ exome AF: 0.670

Gnomad4 EAS exome AF: 0.403

Gnomad4 SAS exome AF: 0.685

Gnomad4 FIN exome AF: 0.666

Gnomad4 NFE exome AF: 0.698

Gnomad4 OTH exome AF: 0.637

GnomAD4 genome AF: 0.554 AC: 84143 AN: 151994 Hom.: 26825 Cov.: 32 AF XY: 0.557 AC XY: 41368 AN XY: 74286

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.689

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.599

Alfa AF: 0.662 Hom.: 30198

Bravo AF: 0.540

Asia WGS AF: 0.537 AC: 1867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.94
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs482284; hg19: chr17-38504241;