4-70518771-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

AMTN Gene-Disease associations (from GenCC):

• amelogenesis imperfecta, type 3A

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• amelogenesis imperfecta type 3B

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212557.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMTN	NM_212557.4	MANE Select	c.-7C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_997722.1	F1T0L8
	AMTN	NM_212557.4	MANE Select	c.-7C>T		5_prime_UTR	Exon 2 of 9	NP_997722.1	F1T0L8
	AMTN	NM_001286731.2		c.-7C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_001273660.1	Q6UX39-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMTN	ENST00000339336.9	TSL:1 MANE Select	c.-7C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	ENSP00000341013.4	Q6UX39-1
	AMTN	ENST00000504451.1	TSL:1	c.-7C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	ENSP00000422452.1	Q6UX39-2
	AMTN	ENST00000339336.9	TSL:1 MANE Select	c.-7C>T		5_prime_UTR	Exon 2 of 9	ENSP00000341013.4	Q6UX39-1

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

GnomAD2 exomes AF: 0.885 AC: 221546 AN: 250456 AF XY: 0.886

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 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

African (AFR) AF: 0.975 AC: 32361 AN: 33174

American (AMR) AF: 0.843 AC: 37594 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 19694 AN: 25980

East Asian (EAS) AF: 0.767 AC: 30326 AN: 39526

South Asian (SAS) AF: 0.886 AC: 76028 AN: 85820

European-Finnish (FIN) AF: 0.905 AC: 48277 AN: 53316

Middle Eastern (MID) AF: 0.861 AC: 4927 AN: 5724

European-Non Finnish (NFE) AF: 0.912 AC: 998653 AN: 1094894

Other (OTH) AF: 0.893 AC: 53325 AN: 59742

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

African (AFR) AF: 0.973 AC: 40431 AN: 41558

American (AMR) AF: 0.887 AC: 13540 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.758 AC: 2632 AN: 3472

East Asian (EAS) AF: 0.790 AC: 4086 AN: 5170

South Asian (SAS) AF: 0.883 AC: 4259 AN: 4822

European-Finnish (FIN) AF: 0.894 AC: 9481 AN: 10606

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61759 AN: 68016

Other (OTH) AF: 0.902 AC: 1905 AN: 2112

Alfa AF: 0.904 Hom.: 42774

Bravo AF: 0.914

Asia WGS AF: 0.839 AC: 2916 AN: 3476

EpiCase AF: 0.904

EpiControl AF: 0.910

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	AMTN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.6
DANN	Benign	0.61
PhyloP100		0.66
PromoterAI		-0.018	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28674149; hg19: chr4-71384488;