rs12108539

Variant names:

• chr4-70631370-A-C
• rs12108539
• NM_031889.3:c.55-300A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-70631370-A-C
• chr4-70631370-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_031889.3(ENAM):​c.55-300A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 151,572 control chromosomes in the GnomAD database, including 812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.081 (812 hom., cov: 32)
• Consequence: ENAM NM_031889.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00500
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta type 1B

  Inheritance: AD, SD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• amelogenesis imperfecta type 1C

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• amelogenesis imperfecta type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-70631370-A-C is Benign according to our data. Variant chr4-70631370-A-C is described in ClinVar as [Benign]. Clinvar id is 1287049.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENAM	NM_031889.3	c.55-300A>C		intron_variant	Intron 2 of 8	ENST00000396073.4	NP_114095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENAM	ENST00000396073.4	c.55-300A>C		intron_variant	Intron 2 of 8	1	NM_031889.3	ENSP00000379383.4

Frequencies

GnomAD3 genomes AF: 0.0808 AC: 12235 AN: 151448 Hom.: 809 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0478

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.0190

Gnomad SAS AF: 0.0655

Gnomad FIN AF: 0.0373

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0411

Gnomad OTH AF: 0.0785

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0808 AC: 12253 AN: 151572 Hom.: 812 Cov.: 32 AF XY: 0.0798 AC XY: 5910 AN XY: 74050

African (AFR) AF: 0.181 AC: 7501 AN: 41340

American (AMR) AF: 0.0477 AC: 726 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0677 AC: 234 AN: 3458

East Asian (EAS) AF: 0.0189 AC: 97 AN: 5142

South Asian (SAS) AF: 0.0658 AC: 314 AN: 4772

European-Finnish (FIN) AF: 0.0373 AC: 392 AN: 10516

Middle Eastern (MID) AF: 0.0959 AC: 28 AN: 292

European-Non Finnish (NFE) AF: 0.0411 AC: 2785 AN: 67810

Other (OTH) AF: 0.0768 AC: 162 AN: 2110

Alfa AF: 0.0573 Hom.: 61

Bravo AF: 0.0845

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.54
PhyloP100		0.0050
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: rs12108539; hg19: chr4-71497087;