Variant 16-4797190-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_024589.3(ROGDI):c.*270T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 425,784 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00068 ( 0 hom. )

Consequence

ROGDI
NM_024589.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.574

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 16-4797190-A-G is Benign according to our data. Variant chr16-4797190-A-G is described in ClinVar as [Benign]. Clinvar id is 319395.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00597 (908/152142) while in subpopulation AFR AF= 0.0209 (866/41492). AF 95% confidence interval is 0.0197. There are 5 homozygotes in gnomad4. There are 437 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
ROGDI	NM_024589.3 linkuse as main transcript	c.*270T>C	3_prime_UTR_variant	11/11	ENST00000322048.12	NP_078865.1
ROGDI	XM_006720947.5 linkuse as main transcript	c.*270T>C	3_prime_UTR_variant	11/11		XP_006721010.1
ROGDI	XM_047434636.1 linkuse as main transcript	c.*270T>C	3_prime_UTR_variant	9/9		XP_047290592.1
ROGDI	NR_046480.2 linkuse as main transcript	n.1141T>C	non_coding_transcript_exon_variant	10/10

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
ROGDI	ENST00000322048.12 linkuse as main transcript	c.*270T>C	3_prime_UTR_variant	11/11	1	NM_024589.3	ENSP00000322832	P1
ROGDI	ENST00000591292.5 linkuse as main transcript	n.2463T>C	non_coding_transcript_exon_variant	7/7	2
ROGDI	ENST00000587377.5 linkuse as main transcript	c.*454T>C	3_prime_UTR_variant, NMD_transcript_variant	11/11	5		ENSP00000468343
ROGDI	ENST00000587843.5 linkuse as main transcript	c.*872T>C	3_prime_UTR_variant, NMD_transcript_variant	10/10	2		ENSP00000465970

Frequencies

GnomAD3 genomes

AF:

0.00588

AC:

894

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0206

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

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:

0.0000147

Gnomad OTH

AF:

0.00621

GnomAD4 exome

AF:

0.000676

AC:

185

AN:

273642

Hom.:

Cov.:

AF XY:

0.000632

AC XY:

AN XY:

144070

show subpopulations

Gnomad4 AFR exome

AF:

0.0178

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000683

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000302

Gnomad4 OTH exome

AF:

0.00112

GnomAD4 genome

AF:

0.00597

AC:

908

AN:

152142

Hom.:

Cov.:

AF XY:

0.00588

AC XY:

437

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0209

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.000386

Hom.:

Bravo

AF:

0.00679

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Amelocerebrohypohidrotic syndrome

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over