rs114103417

chr16-4798682-G-A

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.433-15C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,546,160 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0075 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00097 (19 hom.)
• Consequence: ROGDI NM_024589.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.339

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=-0.88).
• BP6: Variant 16-4798682-G-A is Benign according to our data. Variant chr16-4798682-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-4798682-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00745 (1135/152250) while in subpopulation AFR AF= 0.023 (957/41544). AF 95% confidence interval is 0.0218. There are 5 homozygotes in gnomad4. There are 560 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROGDI	NM_024589.3	c.433-15C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000322048.12
ROGDI	XM_006720947.5	c.433-15C>T		splice_polypyrimidine_tract_variant, intron_variant
ROGDI	XM_047434636.1	c.163-15C>T		splice_polypyrimidine_tract_variant, intron_variant
ROGDI	NR_046480.2	n.440-15C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROGDI	ENST00000322048.12	c.433-15C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_024589.3	P1

Frequencies

GnomAD3 genomes AF: 0.00738 AC: 1123 AN: 152132 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0228

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00715

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00226 AC: 350 AN: 155038 Hom.: 1 AF XY: 0.00182 AC XY: 150 AN XY: 82528

Gnomad AFR exome AF: 0.0220

Gnomad AMR exome AF: 0.00138

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000429

Gnomad FIN exome AF: 0.00946

Gnomad NFE exome AF: 0.000206

Gnomad OTH exome AF: 0.000902

GnomAD4 exome AF: 0.000974 AC: 1357 AN: 1393910 Hom.: 19 Cov.: 31 AF XY: 0.000921 AC XY: 634 AN XY: 688722

Gnomad4 AFR exome AF: 0.0233

Gnomad4 AMR exome AF: 0.00199

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000134

Gnomad4 SAS exome AF: 0.0000752

Gnomad4 FIN exome AF: 0.00726

Gnomad4 NFE exome AF: 0.0000815

Gnomad4 OTH exome AF: 0.00220

GnomAD4 genome AF: 0.00745 AC: 1135 AN: 152250 Hom.: 5 Cov.: 33 AF XY: 0.00752 AC XY: 560 AN XY: 74444

Gnomad4 AFR AF: 0.0230

Gnomad4 AMR AF: 0.00490

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00715

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00284 Hom.: 0

Bravo AF: 0.00796

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Amelocerebrohypohidrotic syndrome Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Dec 01, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.5
Dann	Benign	0.91

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: rs114103417; hg19: chr16-4848683;