Variant chr3-25501080-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.307-102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,342,874 control chromosomes in the GnomAD database, including 22,116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3701 hom., cov: 32)

Exomes 𝑓: 0.17 ( 18415 hom. )

Consequence

RARB
NM_000965.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.555

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:

LOC124909356 (HGNC:):

LOC124909356 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 3-25501080-G-A is Benign according to our data. Variant chr3-25501080-G-A is described in ClinVar as [Benign]. Clinvar id is 1258344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARB	NM_000965.5 linkuse as main transcript	c.307-102G>A		intron_variant		ENST00000330688.9	NP_000956.2
LOC124909356	XR_007095847.1 linkuse as main transcript	n.1107C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARB	ENST00000330688.9 linkuse as main transcript	c.307-102G>A		intron_variant		1	NM_000965.5	ENSP00000332296	P1	P10826-2

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32221

AN:

151854

Hom.:

3700

Cov.:

show subpopulations

Gnomad AFR

AF:

0.306

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.225

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.173

AC:

206287

AN:

1190902

Hom.:

18415

AF XY:

0.174

AC XY:

102313

AN XY:

587564

show subpopulations

Gnomad4 AFR exome

AF:

0.307

Gnomad4 AMR exome

AF:

0.177

Gnomad4 ASJ exome

AF:

0.229

Gnomad4 EAS exome

AF:

0.191

Gnomad4 SAS exome

AF:

0.202

Gnomad4 FIN exome

AF:

0.166

Gnomad4 NFE exome

AF:

0.165

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.212

AC:

32260

AN:

151972

Hom.:

3701

Cov.:

AF XY:

0.212

AC XY:

15721

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.306

Gnomad4 AMR

AF:

0.189

Gnomad4 ASJ

AF:

0.225

Gnomad4 EAS

AF:

0.201

Gnomad4 SAS

AF:

0.206

Gnomad4 FIN

AF:

0.168

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.215

Alfa

AF:

0.186

Hom.:

747

Bravo

AF:

0.217

Asia WGS

AF:

0.206

AC:

716

AN:

3478

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	clinical testing	GeneDx	May 14, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.25

DANN

Benign

0.62

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