9-74498003-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006914.4(RORB):c.7+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,607,328 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (21 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (24 hom.)
• Consequence: RORB NM_006914.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.210

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 9-74498003-C-T is Benign according to our data. Variant chr9-74498003-C-T is described in ClinVar as [Benign]. Clinvar id is 1610805.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1583/152188) while in subpopulation AFR AF= 0.0364 (1510/41526). AF 95% confidence interval is 0.0348. There are 21 homozygotes in gnomad4. There are 727 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1571 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RORB	NM_006914.4	c.7+20C>T		intron_variant		ENST00000376896.8
RORB-AS1	NR_125791.1	n.312+239G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RORB	ENST00000376896.8	c.7+20C>T		intron_variant		1	NM_006914.4	P1
RORB-AS1	ENST00000417576.2	n.886+239G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1571 AN: 152070 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.0362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00265 AC: 632 AN: 238444 Hom.: 6 AF XY: 0.00188 AC XY: 244 AN XY: 129934

Gnomad AFR exome AF: 0.0372

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000335

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00137

GnomAD4 exome AF: 0.00113 AC: 1650 AN: 1455140 Hom.: 24 Cov.: 30 AF XY: 0.000945 AC XY: 684 AN XY: 723778

Gnomad4 AFR exome AF: 0.0380

Gnomad4 AMR exome AF: 0.00156

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000350

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000105

Gnomad4 OTH exome AF: 0.00281

GnomAD4 genome AF: 0.0104 AC: 1583 AN: 152188 Hom.: 21 Cov.: 32 AF XY: 0.00977 AC XY: 727 AN XY: 74408

Gnomad4 AFR AF: 0.0364

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.000731 Hom.: 1

Bravo AF: 0.0113

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

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	14
Dann	Benign	0.88

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: rs113780851; hg19: chr9-77112919;