chr17-40351852-G-T

Position:

• chr17-40351852-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000964.4(RARA):​c.470-58G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 1,571,084 control chromosomes in the GnomAD database, including 1,414 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 0.028 (101 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1313 hom.)
• Consequence: RARA NM_000964.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0282 (4300/152254) while in subpopulation NFE AF= 0.0449 (3055/67988). AF 95% confidence interval is 0.0436. There are 101 homozygotes in gnomad4. There are 2077 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4300 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARA	NM_000964.4	c.470-58G>T		intron_variant		ENST00000254066.10	NP_000955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARA	ENST00000254066.10	c.470-58G>T		intron_variant		1	NM_000964.4	ENSP00000254066.5

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4304 AN: 152136 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.00707

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0182

GnomAD4 exome AF: 0.0403 AC: 57111 AN: 1418830 Hom.: 1313 AF XY: 0.0399 AC XY: 28124 AN XY: 705554

Gnomad4 AFR exome AF: 0.00591

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.0384

Gnomad4 EAS exome AF: 0.000154

Gnomad4 SAS exome AF: 0.0245

Gnomad4 FIN exome AF: 0.0436

Gnomad4 NFE exome AF: 0.0447

Gnomad4 OTH exome AF: 0.0396

GnomAD4 genome AF: 0.0282 AC: 4300 AN: 152254 Hom.: 101 Cov.: 32 AF XY: 0.0279 AC XY: 2077 AN XY: 74436

Gnomad4 AFR AF: 0.00705

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0213

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0449

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0335 Hom.: 58

Bravo AF: 0.0243

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.87

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: rs4890109; hg19: chr17-38508104; COSMIC: COSV54189999; COSMIC: COSV54189999;