dbSNP rs7821494: FAM83H:c.448-138G>C (chr8-143729461-C-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_198488.5(FAM83H):c.448-138G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 938,528 control chromosomes in the GnomAD database, including 27,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 4895 hom., cov: 32)

Exomes 𝑓: 0.23 ( 22423 hom. )

Consequence

FAM83H
NM_198488.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.372

Publications

4 publications found

Variant links:

Genes affected

FAM83H (HGNC:24797): (family with sequence similarity 83 member H) The protein encoded by this gene plays an important role in the structural development and calcification of tooth enamel. Defects in this gene are a cause of amelogenesis imperfecta type 3 (AI3). [provided by RefSeq, Mar 2010]

FAM83H Gene-Disease associations (from GenCC):

amelogenesis imperfecta, type 3A
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

FAM83H 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=-0.9).

BP6

Variant 8-143729461-C-G is Benign according to our data. Variant chr8-143729461-C-G is described in ClinVar as Benign. ClinVar VariationId is 1279352.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM83H	NM_198488.5 link	c.448-138G>C		intron_variant	Intron 2 of 4	ENST00000388913.4	NP_940890.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM83H	ENST00000388913.4 link	c.448-138G>C		intron_variant	Intron 2 of 4	5	NM_198488.5	ENSP00000373565.3
FAM83H	ENST00000650760.1 link	c.1051-138G>C		intron_variant	Intron 2 of 4			ENSP00000499217.1

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37226

AN:

151900

Hom.:

4883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.0813

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.516

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.318

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.243

GnomAD4 exome

AF:

0.225

AC:

177087

AN:

786510

Hom.:

22423

AF XY:

0.226

AC XY:

92072

AN XY:

406510

show subpopulations

African (AFR)

AF:

0.276

AC:

5506

AN:

19936

American (AMR)

AF:

0.299

AC:

10067

AN:

33638

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

4404

AN:

19970

East Asian (EAS)

AF:

0.495

AC:

16293

AN:

32914

South Asian (SAS)

AF:

0.253

AC:

16420

AN:

64880

European-Finnish (FIN)

AF:

0.254

AC:

9321

AN:

36730

Middle Eastern (MID)

AF:

0.277

AC:

817

AN:

2946

European-Non Finnish (NFE)

AF:

0.196

AC:

105228

AN:

537726

Other (OTH)

AF:

0.239

AC:

9031

AN:

37770

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

7736

15471

23207

30942

38678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2484

4968

7452

9936

12420

<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:

0.245

AC:

37275

AN:

152018

Hom.:

4895

Cov.:

AF XY:

0.250

AC XY:

18559

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.275

AC:

11394

AN:

41440

American (AMR)

AF:

0.251

AC:

3843

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

785

AN:

3468

East Asian (EAS)

AF:

0.517

AC:

2657

AN:

5144

South Asian (SAS)

AF:

0.270

AC:

1302

AN:

4818

European-Finnish (FIN)

AF:

0.256

AC:

2702

AN:

10572

Middle Eastern (MID)

AF:

0.312

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.204

AC:

13901

AN:

67976

Other (OTH)

AF:

0.249

AC:

526

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1399

2798

4196

5595

6994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<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:

0.124

Hom.:

214

Bravo

AF:

0.249

Asia WGS

AF:

0.399

AC:

1385

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.4

(source)

DANN

Benign

0.62

PhyloP100

0.37

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over