Variant rs7680880 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_016519.6(AMBN):c.1323A>G(p.Ala441Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,612,720 control chromosomes in the GnomAD database, including 19,981 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.23 ( 7952 hom., cov: 32)

Exomes 𝑓: 0.095 ( 12029 hom. )

Consequence

AMBN
NM_016519.6 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.52

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 4-70606709-A-G is Benign according to our data. Variant chr4-70606709-A-G is described in ClinVar as [Benign]. Clinvar id is 3059474.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-3.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMBN	NM_016519.6 link	c.1323A>G	p.Ala441Ala	synonymous_variant	13/13	ENST00000322937.10	NP_057603.1	Q9NP70-1Q546D7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMBN	ENST00000322937.10 link	c.1323A>G	p.Ala441Ala	synonymous_variant	13/13	1	NM_016519.6	ENSP00000313809.6		Q9NP70-1
AMBN	ENST00000449493.2 link	c.1278A>G	p.Ala426Ala	synonymous_variant	13/13	5		ENSP00000391234.2		Q9NP70-2

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35291

AN:

152046

Hom.:

7922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.590

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.0917

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0757

Gnomad OTH

AF:

0.198

GnomAD3 exomes

AF:

0.129

AC:

32085

AN:

248236

Hom.:

4147

AF XY:

0.123

AC XY:

16573

AN XY:

134780

show subpopulations

Gnomad AFR exome

AF:

0.607

Gnomad AMR exome

AF:

0.0938

Gnomad ASJ exome

AF:

0.0919

Gnomad EAS exome

AF:

0.140

Gnomad SAS exome

AF:

0.160

Gnomad FIN exome

AF:

0.106

Gnomad NFE exome

AF:

0.0729

Gnomad OTH exome

AF:

0.110

GnomAD4 exome

AF:

0.0948

AC:

138464

AN:

1460556

Hom.:

12029

Cov.:

AF XY:

0.0950

AC XY:

69042

AN XY:

726514

show subpopulations

Gnomad4 AFR exome

AF:

0.609

Gnomad4 AMR exome

AF:

0.102

Gnomad4 ASJ exome

AF:

0.0899

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.102

Gnomad4 NFE exome

AF:

0.0700

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.232

AC:

35377

AN:

152164

Hom.:

7952

Cov.:

AF XY:

0.233

AC XY:

17302

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.590

Gnomad4 AMR

AF:

0.145

Gnomad4 ASJ

AF:

0.0917

Gnomad4 EAS

AF:

0.143

Gnomad4 SAS

AF:

0.160

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.0757

Gnomad4 OTH

AF:

0.196

Alfa

AF:

0.108

Hom.:

3897

Bravo

AF:

0.249

Asia WGS

AF:

0.210

AC:

729

AN:

3478

EpiCase

AF:

0.0755

EpiControl

AF:

0.0738

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

AMBN-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 13, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.075

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over