rs2715553

Positions:

• chr17-40340068-G-A
• chr17-40340068-G-C

Variant summary

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

The NM_000964.4(RARA):​c.179-8248G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 151,968 control chromosomes in the GnomAD database, including 31,038 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 0.62 (31038 hom., cov: 31)
• Consequence: RARA NM_000964.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARA	NM_000964.4	c.179-8248G>A		intron_variant		ENST00000254066.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARA	ENST00000254066.10	c.179-8248G>A		intron_variant		1	NM_000964.4	P4
RARA	ENST00000425707.7	c.178+8672G>A		intron_variant		1
RARA	ENST00000394089.6	c.179-8248G>A		intron_variant		2		P4
RARA	ENST00000577646.5	c.179-8248G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94046 AN: 151850 Hom.: 30967 Cov.: 31

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.547

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.620 AC: 94172 AN: 151968 Hom.: 31038 Cov.: 31 AF XY: 0.611 AC XY: 45375 AN XY: 74242

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.547

Gnomad4 OTH AF: 0.582

Alfa AF: 0.547 Hom.: 29048

Bravo AF: 0.625

Asia WGS AF: 0.529 AC: 1840 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	6.0
DANN	Benign	0.60

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: rs2715553; hg19: chr17-38496320;