Variant rs2229773 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000254066.10(RARA):c.*2C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 1,549,578 control chromosomes in the GnomAD database, including 367 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 0.015 ( 29 hom., cov: 33)

Exomes 𝑓: 0.021 ( 338 hom. )

Consequence

RARA
ENST00000254066.10 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.228

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0151 (2298/152282) while in subpopulation NFE AF= 0.0228 (1548/68002). AF 95% confidence interval is 0.0218. There are 29 homozygotes in gnomad4. There are 1139 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2298 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARA	NM_000964.4 linkuse as main transcript	c.*2C>T		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 linkuse as main transcript	c.*2C>T		3_prime_UTR_variant	9/9	1	NM_000964.4	ENSP00000254066	P4	P10276-1

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2299

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00372

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0179

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.0230

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0228

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0138

AC:

1994

AN:

144368

Hom.:

AF XY:

0.0134

AC XY:

1048

AN XY:

78100

show subpopulations

Gnomad AFR exome

AF:

0.00299

Gnomad AMR exome

AF:

0.00798

Gnomad ASJ exome

AF:

0.00585

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00478

Gnomad FIN exome

AF:

0.0245

Gnomad NFE exome

AF:

0.0223

Gnomad OTH exome

AF:

0.0177

GnomAD4 exome

AF:

0.0208

AC:

29011

AN:

1397296

Hom.:

338

Cov.:

AF XY:

0.0204

AC XY:

14069

AN XY:

689196

show subpopulations

Gnomad4 AFR exome

AF:

0.00320

Gnomad4 AMR exome

AF:

0.00883

Gnomad4 ASJ exome

AF:

0.00588

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00567

Gnomad4 FIN exome

AF:

0.0222

Gnomad4 NFE exome

AF:

0.0239

Gnomad4 OTH exome

AF:

0.0183

GnomAD4 genome

AF:

0.0151

AC:

2298

AN:

152282

Hom.:

Cov.:

AF XY:

0.0153

AC XY:

1139

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00371

Gnomad4 AMR

AF:

0.0178

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00517

Gnomad4 FIN

AF:

0.0230

Gnomad4 NFE

AF:

0.0228

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.0184

Hom.:

Bravo

AF:

0.0138

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Meniere disease

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Meniere Disease Neuroscience Research Program, Faculty of Medicine and Health, Kolling Institute, The University of Sydney

Jan 09, 2024

The NC_000017.11:g.40356228C>T, is a downstream variant in GJD3 gene. The variant is part of an haplotype involved in Meniere’s Disease, composed by g.40356228C>T, g.40363058C>G, g.40363293G>A, g.40363294C>G and g.40363579G>T. The haplotype was found in 10 individuals with familial Meniere’s Disease, segregating in 3 of these families (PP1); and in another 8 individuals with sporadic Meniere’s Disease. The position is not conserved (phyloP = 0.228) (BP4). In summary, this variant meets the criteria to be classified as uncertain significance based on the ACMG/AMP criteria applied: PP1, BP4. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

6.1

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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