NM_006914.4:c.7+1375G>A

Variant names:

• chr9-74499358-G-A
• rs10869406
• NM_006914.4:c.7+1375G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006914.4(RORB):​c.7+1375G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,844 control chromosomes in the GnomAD database, including 13,156 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 0.41 (13156 hom., cov: 31)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.527
• Publications: 8 publications found

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]

RORB-AS1 (HGNC:49803): (RORB antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006914.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORB	NM_006914.4	MANE Select	c.7+1375G>A		intron	N/A	NP_008845.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RORB	ENST00000376896.8	TSL:1 MANE Select	c.7+1375G>A		intron	N/A	ENSP00000366093.2
	RORB-AS1	ENST00000417576.2	TSL:5	n.-231C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62021 AN: 151726 Hom.: 13164 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.409 AC: 62046 AN: 151844 Hom.: 13156 Cov.: 31 AF XY: 0.413 AC XY: 30615 AN XY: 74202

African (AFR) AF: 0.408 AC: 16905 AN: 41408

American (AMR) AF: 0.395 AC: 6035 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1563 AN: 3468

East Asian (EAS) AF: 0.839 AC: 4288 AN: 5108

South Asian (SAS) AF: 0.501 AC: 2408 AN: 4806

European-Finnish (FIN) AF: 0.399 AC: 4198 AN: 10534

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25529 AN: 67920

Other (OTH) AF: 0.398 AC: 839 AN: 2108

Alfa AF: 0.383 Hom.: 12484

Bravo AF: 0.411

Asia WGS AF: 0.573 AC: 1992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.4
DANN	Benign	0.91
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10869406; hg19: chr9-77114274;