Genetic Variant NM_016519.6:c.657A>G (chr4-70603268-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_016519.6(AMBN):c.657A>G(p.Gln219Gln) 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

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

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

AMBN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016519.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMBN	NM_016519.6	MANE Select	c.657A>G	p.Gln219Gln	synonymous	Exon 10 of 13	NP_057603.1	Q9NP70-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMBN	ENST00000322937.10	TSL:1 MANE Select	c.657A>G	p.Gln219Gln	synonymous	Exon 10 of 13	ENSP00000313809.6	Q9NP70-1
	AMBN	ENST00000449493.2	TSL:5	c.612A>G	p.Gln204Gln	synonymous	Exon 10 of 13	ENSP00000391234.2	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

GnomAD2 exomes

AF:

0.153

AC:

38192

AN:

250438

AF XY:

0.154

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 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

African (AFR)

AF:

0.0550

AC:

1841

AN:

33454

American (AMR)

AF:

0.0843

AC:

3768

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

3259

AN:

26114

East Asian (EAS)

AF:

0.0126

AC:

499

AN:

39576

South Asian (SAS)

AF:

0.0704

AC:

6069

AN:

86176

European-Finnish (FIN)

AF:

0.198

AC:

10566

AN:

53344

Middle Eastern (MID)

AF:

0.0485

AC:

279

AN:

5758

European-Non Finnish (NFE)

AF:

0.234

AC:

259710

AN:

1110400

Other (OTH)

AF:

0.176

AC:

10631

AN:

60288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

10830

21659

32489

43318

54148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8542

17084

25626

34168

42710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.154

AC:

23492

AN:

152198

Hom.:

2394

Cov.:

AF XY:

0.149

AC XY:

11107

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0623

AC:

2587

AN:

41538

American (AMR)

AF:

0.108

AC:

1657

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

410

AN:

3468

East Asian (EAS)

AF:

0.00597

AC:

AN:

5194

South Asian (SAS)

AF:

0.0702

AC:

339

AN:

4828

European-Finnish (FIN)

AF:

0.192

AC:

2029

AN:

10572

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.232

AC:

15786

AN:

67986

Other (OTH)

AF:

0.128

AC:

270

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

980

1961

2941

3922

4902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

256

512

768

1024

1280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.195

Hom.:

3010

Bravo

AF:

0.143

Asia WGS

AF:

0.0480

AC:

166

AN:

3472

EpiCase

AF:

0.203

EpiControl

AF:

0.201

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

AMBN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.9

(source)

DANN

Benign

0.40

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over