4-70518771-C-T

Variant names:

• chr4-70518771-C-T
• rs28674149
• NM_212557.4:c.-7C>T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_212557.4(AMTN):​c.-7C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 1,594,978 control chromosomes in the GnomAD database, including 651,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.91 (63754 hom., cov: 31)
  • Exomes 𝑓: 0.90 (587914 hom.)
• Consequence: AMTN NM_212557.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.663

Genes affected

AMTN (HGNC:33188): (amelotin) The mineralized portions of teeth, the dentin and enamel, are formed by mesenchyme-derived odontoblasts and epithelium-derived ameloblasts, respectively. As ameloblasts differentiate, they deposit specific proteins necessary for enamel formation, including amelogenin (AMELX; MIM 300391), enamelin (ENAM; MIM 606585), and ameloblastin (AMBN; MIM 601259), in the organic enamel matrix. Amelotin is specifically expressed in maturation-stage ameloblasts (Iwasaki et al., 2005 [PubMed 16304441]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 4-70518771-C-T is Benign according to our data. Variant chr4-70518771-C-T is described in ClinVar as [Benign]. Clinvar id is 3059340.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.965 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMTN	NM_212557.4	c.-7C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 9	ENST00000339336.9	NP_997722.1
AMTN	NM_212557.4	c.-7C>T		5_prime_UTR_variant	Exon 2 of 9	ENST00000339336.9	NP_997722.1
AMTN	NM_001286731.2	c.-7C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 9		NP_001273660.1
AMTN	NM_001286731.2	c.-7C>T		5_prime_UTR_variant	Exon 2 of 9		NP_001273660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMTN	ENST00000339336	c.-7C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 9	1	NM_212557.4	ENSP00000341013.4
AMTN	ENST00000504451	c.-7C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 9	1		ENSP00000422452.1
AMTN	ENST00000339336	c.-7C>T		5_prime_UTR_variant	Exon 2 of 9	1	NM_212557.4	ENSP00000341013.4
AMTN	ENST00000504451	c.-7C>T		5_prime_UTR_variant	Exon 2 of 9	1		ENSP00000422452.1

Frequencies

GnomAD3 genomes AF: 0.914 AC: 138987 AN: 152108 Hom.: 63702 Cov.: 31

Gnomad AFR AF: 0.973

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.894

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.900

GnomAD3 exomes AF: 0.885 AC: 221546 AN: 250456 Hom.: 98277 AF XY: 0.886 AC XY: 120049 AN XY: 135436

Gnomad AFR exome AF: 0.975

Gnomad AMR exome AF: 0.835

Gnomad ASJ exome AF: 0.762

Gnomad EAS exome AF: 0.795

Gnomad SAS exome AF: 0.884

Gnomad FIN exome AF: 0.902

Gnomad NFE exome AF: 0.909

Gnomad OTH exome AF: 0.881

GnomAD4 exome AF: 0.902 AC: 1301185 AN: 1442752 Hom.: 587914 Cov.: 30 AF XY: 0.901 AC XY: 647732 AN XY: 718900

Gnomad4 AFR exome AF: 0.975

Gnomad4 AMR exome AF: 0.843

Gnomad4 ASJ exome AF: 0.758

Gnomad4 EAS exome AF: 0.767

Gnomad4 SAS exome AF: 0.886

Gnomad4 FIN exome AF: 0.905

Gnomad4 NFE exome AF: 0.912

Gnomad4 OTH exome AF: 0.893

GnomAD4 genome AF: 0.914 AC: 139095 AN: 152226 Hom.: 63754 Cov.: 31 AF XY: 0.911 AC XY: 67839 AN XY: 74428

Gnomad4 AFR AF: 0.973

Gnomad4 AMR AF: 0.887

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.790

Gnomad4 SAS AF: 0.883

Gnomad4 FIN AF: 0.894

Gnomad4 NFE AF: 0.908

Gnomad4 OTH AF: 0.902

Alfa AF: 0.901 Hom.: 37502

Bravo AF: 0.914

Asia WGS AF: 0.839 AC: 2916 AN: 3476

EpiCase AF: 0.904

EpiControl AF: 0.910

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

AMTN-related disorder Benign:1

Mar 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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_noAF	Benign	-0.66
CADD	Benign	8.6
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs28674149; hg19: chr4-71384488;