rs200828005

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_005245.4(FAT1):c.4336G>A(p.Val1446Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,612,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00073 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

FAT1
NM_005245.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 7.91

Publications

0 publications found

Variant links:

Genes affected

FAT1 (HGNC:3595): (FAT atypical cadherin 1) This gene is an ortholog of the Drosophila fat gene, which encodes a tumor suppressor essential for controlling cell proliferation during Drosophila development. The gene product is a member of the cadherin superfamily, a group of integral membrane proteins characterized by the presence of cadherin-type repeats. In addition to containing 34 tandem cadherin-type repeats, the gene product has five epidermal growth factor (EGF)-like repeats and one laminin A-G domain. This gene is expressed at high levels in a number of fetal epithelia. Its product probably functions as an adhesion molecule and/or signaling receptor, and is likely to be important in developmental processes and cell communication. Transcript variants derived from alternative splicing and/or alternative promoter usage exist, but they have not been fully described. [provided by RefSeq, Jul 2008]

FAT1 Gene-Disease associations (from GenCC):

focal segmental glomerulosclerosis
Inheritance: AR Classification: STRONG Submitted by: ClinGen

FAT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024121523).

BP6

Variant 4-186628751-C-T is Benign according to our data. Variant chr4-186628751-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 221920.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000729 (111/152284) while in subpopulation AFR AF = 0.00253 (105/41550). AF 95% confidence interval is 0.00214. There are 0 homozygotes in GnomAd4. There are 53 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005245.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAT1	NM_005245.4	MANE Select	c.4336G>A	p.Val1446Ile	missense	Exon 8 of 27	NP_005236.2	Q14517
FAT1	NM_001440456.1		c.4336G>A	p.Val1446Ile	missense	Exon 8 of 28	NP_001427385.1
FAT1	NM_001440457.1		c.4336G>A	p.Val1446Ile	missense	Exon 8 of 28	NP_001427386.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAT1	ENST00000441802.7	TSL:5 MANE Select	c.4336G>A	p.Val1446Ile	missense	Exon 8 of 27	ENSP00000406229.2	Q14517
FAT1	ENST00000917425.1		c.4336G>A	p.Val1446Ile	missense	Exon 8 of 27	ENSP00000587484.1
FAT1	ENST00000917424.1		c.4336G>A	p.Val1446Ile	missense	Exon 8 of 27	ENSP00000587483.1

Frequencies

GnomAD3 genomes

AF:

0.000729

AC:

111

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000110

AC:

AN:

246274

AF XY:

0.0000972

show subpopulations

Gnomad AFR exome

AF:

0.00164

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000568

AC:

AN:

1460460

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

726536

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

33456

American (AMR)

AF:

0.0000671

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86178

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52904

Middle Eastern (MID)

AF:

0.000180

AC:

AN:

5542

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111584

Other (OTH)

AF:

0.000182

AC:

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000729

AC:

111

AN:

152284

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.00253

AC:

105

AN:

41550

American (AMR)

AF:

0.000261

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000261

Hom.:

Bravo

AF:

0.000706

ESP6500AA

AF:

0.00218

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000232

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Irido-corneo-trabecular dysgenesis;C5680330:Anophthalmia-microphthalmia syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Pathogenic

0.68

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.021

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.36

MutationAssessor

Benign

2.0

PhyloP100

7.9

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.75

REVEL

Uncertain

0.32

Sift

Benign

0.10

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.65

MVP

0.58

MPC

0.41

ClinPred

0.077

GERP RS

5.5

Varity_R

0.11

gMVP

0.29

Mutation Taster

=49/51

disease causing

(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