16-4797706-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_024589.3(ROGDI):c.822+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,225,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

ROGDI
NM_024589.3 splice_region, intron

Scores

Splicing: ADA: 0.0001912

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: -3.03

Publications

0 publications found

Variant links:

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]

ROGDI Gene-Disease associations (from GenCC):

amelocerebrohypohidrotic syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ROGDI links:

ENSG00000285952 (HGNC:):

ENSG00000285952 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01217407).

BP6

Variant 16-4797706-G-A is Benign according to our data. Variant chr16-4797706-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 416250.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00144 (64/44408) while in subpopulation AFR AF = 0.00644 (63/9784). AF 95% confidence interval is 0.00516. There are 0 homozygotes in GnomAd4. There are 31 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ROGDI	NM_024589.3 link	c.822+8C>T	splice_region_variant, intron_variant	Intron 10 of 10	ENST00000322048.12	NP_078865.1	Q9GZN7
ROGDI	NR_046480.2 link	n.829+8C>T	splice_region_variant, intron_variant	Intron 9 of 9
ROGDI	XM_006720947.5 link	c.843+8C>T	splice_region_variant, intron_variant	Intron 10 of 10		XP_006721010.1
ROGDI	XM_047434636.1 link	c.573+8C>T	splice_region_variant, intron_variant	Intron 8 of 8		XP_047290592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROGDI	ENST00000322048.12 link	c.822+8C>T		splice_region_variant, intron_variant	Intron 10 of 10	1	NM_024589.3	ENSP00000322832.6		Q9GZN7

Frequencies

GnomAD3 genomes

AF:

0.00144

AC:

AN:

44408

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00644

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000472

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000120

AC:

AN:

225584

AF XY:

0.0000974

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000290

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000516

AC:

AN:

1181048

Hom.:

Cov.:

AF XY:

0.0000465

AC XY:

AN XY:

580438

show subpopulations

African (AFR)

AF:

0.00134

AC:

AN:

24660

American (AMR)

AF:

0.00

AC:

AN:

31672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17232

East Asian (EAS)

AF:

0.0000419

AC:

AN:

23880

South Asian (SAS)

AF:

0.0000169

AC:

AN:

59334

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34320

Middle Eastern (MID)

AF:

0.000224

AC:

AN:

4462

European-Non Finnish (NFE)

AF:

0.0000234

AC:

AN:

942052

Other (OTH)

AF:

0.0000691

AC:

AN:

43436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00144

AC:

AN:

44408

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

AN XY:

22012

show subpopulations

African (AFR)

AF:

0.00644

AC:

AN:

9784

American (AMR)

AF:

0.00

AC:

AN:

3662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1038

East Asian (EAS)

AF:

0.00

AC:

AN:

2424

South Asian (SAS)

AF:

0.00

AC:

AN:

1536

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3634

Middle Eastern (MID)

AF:

0.00

AC:

AN:

116

European-Non Finnish (NFE)

AF:

0.0000472

AC:

AN:

21188

Other (OTH)

AF:

0.00

AC:

AN:

636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000395

Hom.:

Bravo

AF:

0.000491

ESP6500AA

AF:

0.00228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Amelocerebrohypohidrotic syndrome

Uncertain:1Benign:1

Aug 18, 2022

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.2% (34/16696) (https://gnomad.broadinstitute.org/variant/16-4847707-G-A?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:416250). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is an intronic variant with no predicted change in the amino acid sequence but may have an unknown effect on splicing. Splice prediction tools do not suggest that this variant may affect splicing. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

Jan 17, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Uncertain:1

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ROGDI: PM2, BP4 -

ROGDI-related disorder

Benign:1

Apr 11, 2022

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.061

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.0056

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.29

MetaRNN

Benign

0.012

PhyloP100

-3.0

MVP

0.15

GERP RS

-6.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00019

dbscSNV1_RF

Benign

0.080

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over