Variant 4-70628902-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_031889.3(ENAM):c.-123G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,420 control chromosomes in the GnomAD database, including 9,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 9074 hom., cov: 32)

Exomes 𝑓: 0.040 ( 0 hom. )

Consequence

ENAM
NM_031889.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.02

Variant links:

Genes affected

ENAM (HGNC:3344): (enamelin) Dental enamel forms the outer cap of teeth and is the hardest substance found in vertebrates. This gene encodes the largest protein in the enamel matrix of developing teeth. The protein is involved in the mineralization and structural organization of enamel. Defects in this gene result in amelogenesis imperfect type 1C.[provided by RefSeq, Oct 2009]

ENAM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 4-70628902-G-A is Benign according to our data. Variant chr4-70628902-G-A is described in ClinVar as [Benign]. Clinvar id is 349489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENAM	NM_031889.3 linkuse as main transcript	c.-123G>A		5_prime_UTR_variant	1/9	ENST00000396073.4	NP_114095.2	Q9NRM1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENAM	ENST00000396073 linkuse as main transcript	c.-123G>A		5_prime_UTR_variant	1/9	1	NM_031889.3	ENSP00000379383.4		Q9NRM1

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33210

AN:

151882

Hom.:

9025

Cov.:

show subpopulations

Gnomad AFR

AF:

0.648

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.0190

Gnomad SAS

AF:

0.0678

Gnomad FIN

AF:

0.0378

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.0446

Gnomad OTH

AF:

0.189

GnomAD4 exome

AF:

0.0405

AC:

AN:

420

Hom.:

Cov.:

AF XY:

0.0402

AC XY:

AN XY:

224

show subpopulations

Gnomad4 AMR exome

AF:

0.0303

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.100

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0409

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.219

AC:

33316

AN:

152000

Hom.:

9074

Cov.:

AF XY:

0.214

AC XY:

15943

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.649

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.0189

Gnomad4 SAS

AF:

0.0681

Gnomad4 FIN

AF:

0.0378

Gnomad4 NFE

AF:

0.0446

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.0257

Hom.:

Bravo

AF:

0.243

Asia WGS

AF:

0.107

AC:

369

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Amelogenesis imperfecta

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

-0.60

CADD

Benign

DANN

Benign

0.88

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