17-40344694-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000964.4(RARA):c.179-3622C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00955 in 152,284 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.0096 (10 hom., cov: 32)
• Consequence: RARA NM_000964.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.126

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-40344694-C-T is Benign according to our data. Variant chr17-40344694-C-T is described in ClinVar as [Benign]. Clinvar id is 2647736.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 1458 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARA	NM_000964.4	c.179-3622C>T		intron_variant		ENST00000254066.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARA	ENST00000254066.10	c.179-3622C>T		intron_variant		1	NM_000964.4	P4

Frequencies

GnomAD3 genomes AF: 0.00958 AC: 1458 AN: 152166 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00903

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00434

Gnomad FIN AF: 0.0102

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.0115

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

GnomAD4 genome AF: 0.00955 AC: 1455 AN: 152284 Hom.: 10 Cov.: 32 AF XY: 0.00905 AC XY: 674 AN XY: 74462

Gnomad4 AFR AF: 0.00255

Gnomad4 AMR AF: 0.00902

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00393

Gnomad4 FIN AF: 0.0102

Gnomad4 NFE AF: 0.0142

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00498 Hom.: 0

Bravo AF: 0.00881

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

RARA: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.3
Dann	Benign	0.57

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: rs112509970; hg19: chr17-38500946;