Variant 3-25461360-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000965.5(RARB):c.306+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 1,610,062 control chromosomes in the GnomAD database, including 2,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 291 hom., cov: 32)

Exomes 𝑓: 0.045 ( 2385 hom. )

Consequence

RARB
NM_000965.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.497

Variant links:

Genes affected

RARB (HGNC:9865): (retinoic acid receptor beta) This gene encodes retinoic acid receptor beta, a member of the thyroid-steroid hormone receptor superfamily of nuclear transcriptional regulators. This receptor localizes to the cytoplasm and to subnuclear compartments. It binds retinoic acid, the biologically active form of vitamin A which mediates cellular signalling in embryonic morphogenesis, cell growth and differentiation. It is thought that this protein limits growth of many cell types by regulating gene expression. The gene was first identified in a hepatocellular carcinoma where it flanks a hepatitis B virus integration site. Alternate promoter usage and differential splicing result in multiple transcript variants. [provided by RefSeq, Mar 2014]

RARB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-25461360-G-A is Benign according to our data. Variant chr3-25461360-G-A is described in ClinVar as [Benign]. Clinvar id is 1274651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARB	NM_000965.5 linkuse as main transcript	c.306+19G>A		intron_variant		ENST00000330688.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000330688.9 linkuse as main transcript	c.306+19G>A		intron_variant		1	NM_000965.5	P1	P10826-2

Frequencies

GnomAD3 genomes

AF:

0.0437

AC:

6653

AN:

152080

Hom.:

290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.0536

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.0940

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0350

Gnomad OTH

AF:

0.0456

GnomAD3 exomes

AF:

0.0707

AC:

17446

AN:

246834

Hom.:

1067

AF XY:

0.0688

AC XY:

9166

AN XY:

133302

show subpopulations

Gnomad AFR exome

AF:

0.0113

Gnomad AMR exome

AF:

0.179

Gnomad ASJ exome

AF:

0.0177

Gnomad EAS exome

AF:

0.0603

Gnomad SAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.0983

Gnomad NFE exome

AF:

0.0384

Gnomad OTH exome

AF:

0.0601

GnomAD4 exome

AF:

0.0450

AC:

65605

AN:

1457864

Hom.:

2385

Cov.:

AF XY:

0.0465

AC XY:

33713

AN XY:

725046

show subpopulations

Gnomad4 AFR exome

AF:

0.00956

Gnomad4 AMR exome

AF:

0.173

Gnomad4 ASJ exome

AF:

0.0181

Gnomad4 EAS exome

AF:

0.0427

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.0978

Gnomad4 NFE exome

AF:

0.0346

Gnomad4 OTH exome

AF:

0.0438

GnomAD4 genome

AF:

0.0438

AC:

6667

AN:

152198

Hom.:

291

Cov.:

AF XY:

0.0486

AC XY:

3618

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0117

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.0534

Gnomad4 SAS

AF:

0.106

Gnomad4 FIN

AF:

0.0940

Gnomad4 NFE

AF:

0.0350

Gnomad4 OTH

AF:

0.0475

Alfa

AF:

0.0369

Hom.:

Bravo

AF:

0.0437

Asia WGS

AF:

0.0810

AC:

282

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	GeneDx	May 15, 2021	- -

Microphthalmia, syndromic 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.8

DANN

Benign

0.46

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