Variant 17-40354331-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_000964.4(RARA):c.837C>T(p.Pro279Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00467 in 1,614,144 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 18 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 41 hom. )

Consequence

RARA
NM_000964.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.33

Variant links:

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 links:

RARA (HGNC:):

RARA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 17-40354331-C-T is Benign according to our data. Variant chr17-40354331-C-T is described in ClinVar as [Benign]. Clinvar id is 780426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.33 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0112 (1707/152264) while in subpopulation AFR AF= 0.0321 (1335/41542). AF 95% confidence interval is 0.0307. There are 18 homozygotes in gnomad4. There are 837 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1707 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARA	NM_000964.4 linkuse as main transcript	c.837C>T	p.Pro279Pro	synonymous_variant	7/9	ENST00000254066.10	NP_000955.1	P10276-1Q6I9R7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARA	ENST00000254066.10 linkuse as main transcript	c.837C>T	p.Pro279Pro	synonymous_variant	7/9	1	NM_000964.4	ENSP00000254066.5		P10276-1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1696

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0320

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00354

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00457

AC:

1148

AN:

251250

Hom.:

AF XY:

0.00396

AC XY:

538

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0343

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00399

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00399

AC:

5833

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00380

AC XY:

2762

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0320

Gnomad4 AMR exome

AF:

0.00210

Gnomad4 ASJ exome

AF:

0.00207

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000858

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.00377

Gnomad4 OTH exome

AF:

0.00518

GnomAD4 genome

AF:

0.0112

AC:

1707

AN:

152264

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

837

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0321

Gnomad4 AMR

AF:

0.00503

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00354

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00668

Hom.:

Bravo

AF:

0.0128

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00349

EpiControl

AF:

0.00415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over