rs34367704

Variant names:

• chr4-70605517-G-A
• rs34367704
• NM_016519.6:c.799-668G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-70605517-G-A
• chr4-70605517-G-C

Variant summary

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

The NM_016519.6(AMBN):​c.799-668G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,022 control chromosomes in the GnomAD database, including 5,532 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 0.26 (5532 hom., cov: 32)
• Consequence: AMBN NM_016519.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMBN	NM_016519.6	c.799-668G>A		intron_variant	Intron 12 of 12	ENST00000322937.10	NP_057603.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMBN	ENST00000322937.10	c.799-668G>A		intron_variant	Intron 12 of 12	1	NM_016519.6	ENSP00000313809.6
AMBN	ENST00000449493.2	c.754-668G>A		intron_variant	Intron 12 of 12	5		ENSP00000391234.2

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39293 AN: 151904 Hom.: 5524 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.259 AC: 39331 AN: 152022 Hom.: 5532 Cov.: 32 AF XY: 0.249 AC XY: 18488 AN XY: 74280

African (AFR) AF: 0.251 AC: 10407 AN: 41470

American (AMR) AF: 0.197 AC: 3011 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3468

East Asian (EAS) AF: 0.0184 AC: 95 AN: 5174

South Asian (SAS) AF: 0.146 AC: 706 AN: 4820

European-Finnish (FIN) AF: 0.229 AC: 2418 AN: 10542

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21129 AN: 67962

Other (OTH) AF: 0.209 AC: 441 AN: 2106

Alfa AF: 0.285 Hom.: 8761

Bravo AF: 0.254

Asia WGS AF: 0.113 AC: 395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.46
DANN	Benign	0.74
PhyloP100		-0.69
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: rs34367704; hg19: chr4-71471234;