Variant rs35266919 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.657A>G(p.Gln219=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,611,996 control chromosomes in the GnomAD database, including 35,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.15 ( 2394 hom., cov: 32)

Exomes 𝑓: 0.20 ( 33602 hom. )

Consequence

AMBN
NM_016519.6 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.03

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=-0.6).

BP6

Variant 4-70603268-A-G is Benign according to our data. Variant chr4-70603268-A-G is described in ClinVar as [Benign]. Clinvar id is 3059460.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMBN	NM_016519.6 linkuse as main transcript	c.657A>G	p.Gln219=	synonymous_variant	10/13	ENST00000322937.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMBN	ENST00000322937.10 linkuse as main transcript	c.657A>G	p.Gln219=	synonymous_variant	10/13	1	NM_016519.6	P1	Q9NP70-1
AMBN	ENST00000449493.2 linkuse as main transcript	c.612A>G	p.Gln204=	synonymous_variant	10/13	5			Q9NP70-2

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23484

AN:

152080

Hom.:

2393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0622

Gnomad AMI

AF:

0.398

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.00595

Gnomad SAS

AF:

0.0702

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.153

AC:

38192

AN:

250438

Hom.:

3782

AF XY:

0.154

AC XY:

20813

AN XY:

135460

show subpopulations

Gnomad AFR exome

AF:

0.0570

Gnomad AMR exome

AF:

0.0790

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.00804

Gnomad SAS exome

AF:

0.0689

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.166

GnomAD4 exome

AF:

0.203

AC:

296622

AN:

1459798

Hom.:

33602

Cov.:

AF XY:

0.199

AC XY:

144589

AN XY:

726286

show subpopulations

Gnomad4 AFR exome

AF:

0.0550

Gnomad4 AMR exome

AF:

0.0843

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.0126

Gnomad4 SAS exome

AF:

0.0704

Gnomad4 FIN exome

AF:

0.198

Gnomad4 NFE exome

AF:

0.234

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.154

AC:

23492

AN:

152198

Hom.:

2394

Cov.:

AF XY:

0.149

AC XY:

11107

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0623

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.00597

Gnomad4 SAS

AF:

0.0702

Gnomad4 FIN

AF:

0.192

Gnomad4 NFE

AF:

0.232

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.196

Hom.:

2261

Bravo

AF:

0.143

Asia WGS

AF:

0.0480

AC:

166

AN:

3472

EpiCase

AF:

0.203

EpiControl

AF:

0.201

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

Oct 21, 2019

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

-0.60

CADD

Benign

3.9

DANN

Benign

0.40

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