rs1555574254

Positions:

• chr17-40356061-TCTCATCCAGGAAATGTTGGAGAACTCAGAGGGCCTGGACACTCTGAGCGGACAGCCGGGGGGTGGGGGGCGGGACGGGGGTGGCCTGGCCCCCCCGCCAGGCAGCTGTAGCCCCAGCCTCAGCCCCAGCTCCAACAGAAGCAGCCCGGCCACCCACTCCCCGTGA-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_000964.4(RARA):​c.1226_*1del​(p.Leu409_Ter463delins???) variant causes a stop lost, conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as drug response (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RARA NM_000964.4 stop_lost, conservative_inframe_deletion
• Clinical Significance: drug response no assertion criteria provided O:1
• Conservation: PhyloP100: 8.02

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]

RARA (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_000964.4 Downstream stopcodon found after 150 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARA	NM_000964.4	c.1226_*1del	p.Leu409_Ter463delins???	stop_lost, conservative_inframe_deletion	9/9	ENST00000254066.10	NP_000955.1
RARA	NM_000964.4	c.1226_*1del		3_prime_UTR_variant	9/9	ENST00000254066.10	NP_000955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARA	ENST00000254066.10	c.1226_*1del	p.Leu409_Ter463delins???	stop_lost, conservative_inframe_deletion	9/9	1	NM_000964.4	ENSP00000254066.5
RARA	ENST00000254066.10	c.1226_*1del		3_prime_UTR_variant	9/9	1	NM_000964.4	ENSP00000254066.5

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Tretinoin response Other:1

drug response, no assertion criteria provided

clinical testing

Center for Advanced Molecular Diagnostics, Cytogenetics Laboratory, Brigham and Women's Hospital

Mar 01, 2015

Associated with resistance of acute promyelocytic leukemia to all trans retinoic acid (ATRA) Failure of ATRA therapy

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1555574254; hg19: chr17-38512313;