9-74623944-T-C

Variant names:

• chr9-74623944-T-C
• rs1157358
• NM_006914.4:c.8-6338T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006914.4(RORB):​c.8-6338T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,104 control chromosomes in the GnomAD database, including 45,032 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (45032 hom., cov: 32)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

Genes affected

RORB (HGNC:10259): (RAR related orphan receptor B) The protein encoded by this gene is a member of the NR1 subfamily of nuclear hormone receptors. It is a DNA-binding protein that can bind as a monomer or as a homodimer to hormone response elements upstream of several genes to enhance the expression of those genes. The encoded protein has been shown to interact with NM23-2, a nucleoside diphosphate kinase involved in organogenesis and differentiation, and to help regulate the expression of some genes involved in circadian rhythm. [provided by RefSeq, Feb 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORB	NM_006914.4	c.8-6338T>C		intron_variant	Intron 1 of 9	ENST00000376896.8	NP_008845.2
RORB	NM_001365023.1	c.41-6338T>C		intron_variant	Intron 1 of 9		NP_001351952.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORB	ENST00000376896.8	c.8-6338T>C		intron_variant	Intron 1 of 9	1	NM_006914.4	ENSP00000366093.2
RORB	ENST00000396204.2	c.41-6338T>C		intron_variant	Intron 1 of 9	1		ENSP00000379507.2

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115943 AN: 151986 Hom.: 45013 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.928

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.789

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

GnomAD4 genome AF: 0.763 AC: 116009 AN: 152104 Hom.: 45032 Cov.: 32 AF XY: 0.764 AC XY: 56821 AN XY: 74358

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.906

Gnomad4 EAS AF: 0.927

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.822

Gnomad4 OTH AF: 0.791

Alfa AF: 0.790 Hom.: 5918

Bravo AF: 0.752

Asia WGS AF: 0.851 AC: 2960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.0
DANN	Benign	0.54

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: rs1157358; hg19: chr9-77238860; COSMIC: COSV65334341;