3-25501080-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.555

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]

LOC124909356 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
RARB	NM_000965.5	c.307-102G>A		intron_variant		ENST00000330688.9
LOC124909356	XR_007095847.1	n.1107C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000330688.9	c.307-102G>A		intron_variant		1	NM_000965.5	P1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32221 AN: 151854 Hom.: 3700 Cov.: 32

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

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.: 32 AF XY: 0.212 AC XY: 15721 AN XY: 74280

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

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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

Other links and lift over

dbSNP: rs2116703; hg19: chr3-25542571; COSMIC: COSV58064714;