3-25501097-A-G

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.307-85A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00652 in 1,450,442 control chromosomes in the GnomAD database, including 499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.034 (282 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (217 hom.)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.502

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=-0.82).
• BP6: Variant 3-25501097-A-G is Benign according to our data. Variant chr3-25501097-A-G is described in ClinVar as [Benign]. Clinvar id is 1265767.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARB	NM_000965.5	c.307-85A>G		intron_variant		ENST00000330688.9
LOC124909356	XR_007095847.1	n.1090T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARB	ENST00000330688.9	c.307-85A>G		intron_variant		1	NM_000965.5	P1

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5142 AN: 152150 Hom.: 278 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0254

GnomAD4 exome AF: 0.00331 AC: 4300 AN: 1298174 Hom.: 217 AF XY: 0.00293 AC XY: 1874 AN XY: 640166

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.00925

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000189

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000275

Gnomad4 OTH exome AF: 0.00804

GnomAD4 genome AF: 0.0339 AC: 5164 AN: 152268 Hom.: 282 Cov.: 32 AF XY: 0.0330 AC XY: 2454 AN XY: 74452

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0157 Hom.: 21

Bravo AF: 0.0390

Asia WGS AF: 0.00693 AC: 24 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	-0.82
Cadd	Benign	0.88
Dann	Benign	0.35

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: rs7623934; hg19: chr3-25542588;