4-70605459-G-T

Position:

• chr4-70605459-G-T

Variant summary

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

The NM_016519.6(AMBN):​c.799-726G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 151,998 control chromosomes in the GnomAD database, including 4,721 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 0.24 (4721 hom., cov: 32)
• Consequence: AMBN NM_016519.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

Genes affected

AMBN (HGNC:452): (ameloblastin) This gene encodes the nonamelogenin enamel matrix protein ameloblastin. The encoded protein may be important in enamel matrix formation and mineralization. This gene is located in the calcium-binding phosphoprotein gene cluster on chromosome 4. Mutations in this gene may be associated with dentinogenesis imperfect and autosomal dominant amylogenesis imperfect. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMBN	NM_016519.6	c.799-726G>T		intron_variant		ENST00000322937.10	NP_057603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMBN	ENST00000322937.10	c.799-726G>T		intron_variant		1	NM_016519.6	ENSP00000313809.6
AMBN	ENST00000449493.2	c.754-726G>T		intron_variant		5		ENSP00000391234.2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36201 AN: 151880 Hom.: 4715 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.238 AC: 36227 AN: 151998 Hom.: 4721 Cov.: 32 AF XY: 0.229 AC XY: 17029 AN XY: 74278

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.00945

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.195

Alfa AF: 0.204 Hom.: 693

Bravo AF: 0.236

Asia WGS AF: 0.0780 AC: 273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.34

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: rs34538475; hg19: chr4-71471176;