Variant chr4-70602628-CAGG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PM4_SupportingBP6BA1

The NM_016519.6(AMBN):c.539_541delGAG(p.Gly180del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 1,568,758 control chromosomes in the GnomAD database, including 4,446 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.094 ( 770 hom., cov: 31)

Exomes 𝑓: 0.066 ( 3676 hom. )

Consequence

AMBN
NM_016519.6 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.390

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 -8 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_016519.6. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 4-70602628-CAGG-C is Benign according to our data. Variant chr4-70602628-CAGG-C is described in ClinVar as [Benign]. Clinvar id is 3056626.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMBN	NM_016519.6 linkuse as main transcript	c.539_541delGAG	p.Gly180del	disruptive_inframe_deletion	7/13	ENST00000322937.10	NP_057603.1	Q9NP70-1Q546D7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMBN	ENST00000322937.10 linkuse as main transcript	c.539_541delGAG	p.Gly180del	disruptive_inframe_deletion	7/13	1	NM_016519.6	ENSP00000313809.6		Q9NP70-1
AMBN	ENST00000449493.2 linkuse as main transcript	c.494_496delGAG	p.Gly165del	disruptive_inframe_deletion	7/13	5		ENSP00000391234.2		Q9NP70-2

Frequencies

GnomAD3 genomes

AF:

0.0942

AC:

14294

AN:

151800

Hom.:

771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.0934

Gnomad AMR

AF:

0.0868

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.142

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.0707

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0634

Gnomad OTH

AF:

0.100

GnomAD3 exomes

AF:

0.0812

AC:

19064

AN:

234774

Hom.:

870

AF XY:

0.0808

AC XY:

10300

AN XY:

127502

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.0678

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.126

Gnomad SAS exome

AF:

0.103

Gnomad FIN exome

AF:

0.0669

Gnomad NFE exome

AF:

0.0620

Gnomad OTH exome

AF:

0.0802

GnomAD4 exome

AF:

0.0657

AC:

93066

AN:

1416840

Hom.:

3676

AF XY:

0.0670

AC XY:

47123

AN XY:

703444

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.0694

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.129

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.0642

Gnomad4 NFE exome

AF:

0.0558

Gnomad4 OTH exome

AF:

0.0790

GnomAD4 genome

AF:

0.0942

AC:

14305

AN:

151918

Hom.:

770

Cov.:

AF XY:

0.0951

AC XY:

7060

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.140

Gnomad4 AMR

AF:

0.0865

Gnomad4 ASJ

AF:

0.150

Gnomad4 EAS

AF:

0.142

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.0707

Gnomad4 NFE

AF:

0.0634

Gnomad4 OTH

AF:

0.0994

Alfa

AF:

0.0894

Hom.:

133

Bravo

AF:

0.0967

Asia WGS

AF:

0.132

AC:

455

AN:

3462

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 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

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.21

Position offset: -4

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