rs113858060

chr16-4802372-G-Achr16-4802372-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_024589.3(ROGDI):c.117+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,566,322 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (9 hom., cov: 33)
  • Exomes 𝑓: 0.00063 (17 hom.)
• Consequence: ROGDI NM_024589.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.306

Genes affected

ROGDI (HGNC:29478): (rogdi atypical leucine zipper) Involved in brain development; neurogenesis; and odontogenesis of dentin-containing tooth. Located in nuclear envelope. Implicated in Kohlschutter-Tonz syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 16-4802372-G-A is Benign according to our data. Variant chr16-4802372-G-A is described in ClinVar as [Benign]. Clinvar id is 416248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-4802372-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00674 (1026/152242) while in subpopulation AFR AF= 0.0235 (976/41572). AF 95% confidence interval is 0.0223. There are 9 homozygotes in gnomad4. There are 443 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROGDI	NM_024589.3	c.117+10C>T		intron_variant		ENST00000322048.12
ROGDI	XM_006720947.5	c.117+10C>T		intron_variant
ROGDI	XM_047434636.1	c.-99+10C>T		intron_variant
ROGDI	NR_046480.2	n.179+10C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROGDI	ENST00000322048.12	c.117+10C>T		intron_variant		1	NM_024589.3	P1

Frequencies

GnomAD3 genomes AF: 0.00674 AC: 1025 AN: 152124 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00168 AC: 299 AN: 178084 Hom.: 2 AF XY: 0.00122 AC XY: 120 AN XY: 98040

Gnomad AFR exome AF: 0.0235

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000418

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000520

Gnomad OTH exome AF: 0.000872

GnomAD4 exome AF: 0.000627 AC: 886 AN: 1414080 Hom.: 17 Cov.: 31 AF XY: 0.000555 AC XY: 389 AN XY: 701446

Gnomad4 AFR exome AF: 0.0233

Gnomad4 AMR exome AF: 0.00125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000374

Gnomad4 FIN exome AF: 0.0000215

Gnomad4 NFE exome AF: 0.0000174

Gnomad4 OTH exome AF: 0.00127

GnomAD4 genome AF: 0.00674 AC: 1026 AN: 152242 Hom.: 9 Cov.: 33 AF XY: 0.00595 AC XY: 443 AN XY: 74446

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.000181 Hom.: 0

Bravo AF: 0.00755

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Nov 20, 2017

- -

Amelocerebrohypohidrotic syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	4.0
Dann	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs113858060; hg19: chr16-4852373;