rs12640848

chr4-70640695-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031889.3(ENAM):c.589-1320A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,924 control chromosomes in the GnomAD database, including 21,875 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (21875 hom., cov: 31)
• Consequence: ENAM NM_031889.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENAM	NM_031889.3	c.589-1320A>G		intron_variant		ENST00000396073.4
ENAM	NM_001368133.1	c.-66-1320A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENAM	ENST00000396073.4	c.589-1320A>G		intron_variant		1	NM_031889.3	P1
	ENST00000472903.5	n.99+2852A>G		intron_variant, non_coding_transcript_variant		5
ENAM	ENST00000472597.1	c.-66-1320A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72126 AN: 151806 Hom.: 21885 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.475 AC: 72102 AN: 151924 Hom.: 21875 Cov.: 31 AF XY: 0.466 AC XY: 34573 AN XY: 74200

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.491

Alfa AF: 0.647 Hom.: 41726

Bravo AF: 0.438

Asia WGS AF: 0.310 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.1
Dann	Benign	0.32

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

Other links and lift over

dbSNP: rs12640848; hg19: chr4-71506412;