NM_000965.5:c.157+207C>T

Variant names:

• chr3-25429095-C-T
• rs78541681
• NM_000965.5:c.157+207C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000965.5(RARB):​c.157+207C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 152,144 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.028 (183 hom., cov: 33)
• Consequence: RARB NM_000965.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• microphthalmia, syndromic 12

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Baylor College of Medicine Research Center, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Matthew-Wood syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-25429095-C-T is Benign according to our data. Variant chr3-25429095-C-T is described in ClinVar as Benign. ClinVar VariationId is 1280900.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0933 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000965.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARB	NM_000965.5	MANE Select	c.157+207C>T		intron	N/A	NP_000956.2
	RARB	NM_001290216.3		c.179-32098C>T		intron	N/A	NP_001277145.1	P10826-1
	RARB	NM_001290300.2		c.29-32098C>T		intron	N/A	NP_001277229.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARB	ENST00000330688.9	TSL:1 MANE Select	c.157+207C>T		intron	N/A	ENSP00000332296.4	P10826-2
	RARB	ENST00000437042.7	TSL:1	c.-180+564C>T		intron	N/A	ENSP00000398840.2	P10826-3
	RARB	ENST00000383772.9	TSL:5	c.179-32098C>T		intron	N/A	ENSP00000373282.5	P10826-1

Frequencies

GnomAD3 genomes AF: 0.0278 AC: 4230 AN: 152026 Hom.: 181 Cov.: 33

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000471

Gnomad OTH AF: 0.0221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0279 AC: 4245 AN: 152144 Hom.: 183 Cov.: 33 AF XY: 0.0273 AC XY: 2030 AN XY: 74388

African (AFR) AF: 0.0958 AC: 3972 AN: 41476

American (AMR) AF: 0.0101 AC: 155 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3470

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5176

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4804

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10600

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000471 AC: 32 AN: 68002

Other (OTH) AF: 0.0218 AC: 46 AN: 2108

Alfa AF: 0.0221 Hom.: 16

Bravo AF: 0.0323

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.61
PhyloP100		-1.1
PromoterAI		-0.029	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs78541681; hg19: chr3-25470586;