NM_016519.6:c.295-221C>T

Variant names:

• chr4-70601197-C-T
• rs4694075
• NM_016519.6:c.295-221C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016519.6(AMBN):​c.295-221C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,898 control chromosomes in the GnomAD database, including 21,328 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 0.52 (21328 hom., cov: 31)
• Consequence: AMBN NM_016519.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473
• Publications: 31 publications found

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]

AMBN Gene-Disease associations (from GenCC):

• amelogenesis imperfecta type 1F

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMBN	NM_016519.6	c.295-221C>T		intron_variant	Intron 5 of 12	ENST00000322937.10	NP_057603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMBN	ENST00000322937.10	c.295-221C>T		intron_variant	Intron 5 of 12	1	NM_016519.6	ENSP00000313809.6
AMBN	ENST00000449493.2	c.295-266C>T		intron_variant	Intron 5 of 12	5		ENSP00000391234.2

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78948 AN: 151780 Hom.: 21312 Cov.: 31

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.520 AC: 79013 AN: 151898 Hom.: 21328 Cov.: 31 AF XY: 0.511 AC XY: 37932 AN XY: 74218

African (AFR) AF: 0.653 AC: 27055 AN: 41406

American (AMR) AF: 0.446 AC: 6799 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1510 AN: 3468

East Asian (EAS) AF: 0.571 AC: 2937 AN: 5146

South Asian (SAS) AF: 0.436 AC: 2106 AN: 4830

European-Finnish (FIN) AF: 0.354 AC: 3727 AN: 10542

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33217 AN: 67936

Other (OTH) AF: 0.536 AC: 1129 AN: 2106

Alfa AF: 0.498 Hom.: 32095

Bravo AF: 0.533

Asia WGS AF: 0.498 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.34
PhyloP100		-0.47
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: rs4694075; hg19: chr4-71466914;