16-4797316-C-T

Variant names:

• chr16-4797316-C-T
• rs7546
• NM_024589.3:c.*144G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024589.3(ROGDI):​c.*144G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 716,446 control chromosomes in the GnomAD database, including 67,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13132 hom., cov: 33)
  • Exomes 𝑓: 0.43 (54029 hom.)
• Consequence: ROGDI NM_024589.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00100
• Publications: 21 publications found

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)

ENSG00000285952 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-4797316-C-T is Benign according to our data. Variant chr16-4797316-C-T is described in ClinVar as [Benign]. Clinvar id is 319396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROGDI	NM_024589.3	c.*144G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000322048.12	NP_078865.1
ROGDI	NR_046480.2	n.1015G>A		non_coding_transcript_exon_variant	Exon 10 of 10
ROGDI	XM_006720947.5	c.*144G>A		3_prime_UTR_variant	Exon 11 of 11		XP_006721010.1
ROGDI	XM_047434636.1	c.*144G>A		3_prime_UTR_variant	Exon 9 of 9		XP_047290592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROGDI	ENST00000322048.12	c.*144G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_024589.3	ENSP00000322832.6

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61709 AN: 151974 Hom.: 13114 Cov.: 33

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.424

GnomAD4 exome AF: 0.434 AC: 244761 AN: 564354 Hom.: 54029 Cov.: 8 AF XY: 0.438 AC XY: 128245 AN XY: 293026

African (AFR) AF: 0.270 AC: 3970 AN: 14690

American (AMR) AF: 0.532 AC: 9829 AN: 18470

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 6303 AN: 14100

East Asian (EAS) AF: 0.344 AC: 10731 AN: 31232

South Asian (SAS) AF: 0.496 AC: 23567 AN: 47552

European-Finnish (FIN) AF: 0.436 AC: 16428 AN: 37664

Middle Eastern (MID) AF: 0.409 AC: 890 AN: 2178

European-Non Finnish (NFE) AF: 0.434 AC: 160394 AN: 369182

Other (OTH) AF: 0.432 AC: 12649 AN: 29286

GnomAD4 genome AF: 0.406 AC: 61755 AN: 152092 Hom.: 13132 Cov.: 33 AF XY: 0.409 AC XY: 30404 AN XY: 74350

African (AFR) AF: 0.277 AC: 11515 AN: 41504

American (AMR) AF: 0.507 AC: 7755 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1585 AN: 3472

East Asian (EAS) AF: 0.343 AC: 1774 AN: 5166

South Asian (SAS) AF: 0.491 AC: 2370 AN: 4826

European-Finnish (FIN) AF: 0.443 AC: 4679 AN: 10570

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30742 AN: 67952

Other (OTH) AF: 0.430 AC: 908 AN: 2112

Alfa AF: 0.436 Hom.: 16262

Bravo AF: 0.405

Asia WGS AF: 0.477 AC: 1658 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Amelocerebrohypohidrotic syndrome Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.47
PhyloP100		-0.0010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7546; hg19: chr16-4847317; COSMIC: COSV59021666; COSMIC: COSV59021666;