rs2031197

Variant names:

• chr9-74553832-G-A
• rs2031197
• NM_006914.4:c.7+55849G>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+55849G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 152,034 control chromosomes in the GnomAD database, including 26,511 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 0.58 (26511 hom., cov: 32)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 4 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 Gene-Disease associations (from GenCC):

• epilepsy, idiopathic generalized, susceptibility to, 15

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• epilepsy

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RORB	NM_006914.4	c.7+55849G>A		intron_variant	Intron 1 of 9	ENST00000376896.8	NP_008845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RORB	ENST00000376896.8	c.7+55849G>A		intron_variant	Intron 1 of 9	1	NM_006914.4	ENSP00000366093.2

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88163 AN: 151916 Hom.: 26467 Cov.: 32

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.581 AC: 88270 AN: 152034 Hom.: 26511 Cov.: 32 AF XY: 0.576 AC XY: 42769 AN XY: 74314

African (AFR) AF: 0.722 AC: 29927 AN: 41470

American (AMR) AF: 0.577 AC: 8801 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 1821 AN: 3468

East Asian (EAS) AF: 0.225 AC: 1161 AN: 5162

South Asian (SAS) AF: 0.509 AC: 2447 AN: 4806

European-Finnish (FIN) AF: 0.491 AC: 5192 AN: 10574

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36976 AN: 67978

Other (OTH) AF: 0.571 AC: 1203 AN: 2108

Alfa AF: 0.559 Hom.: 12241

Bravo AF: 0.592

Asia WGS AF: 0.452 AC: 1573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.097
DANN	Benign	0.32
PhyloP100		-1.4
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: rs2031197; hg19: chr9-77168748;