4-186595501-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005245.4(FAT1):c.13138+188A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,068 control chromosomes in the GnomAD database, including 7,167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7167 hom., cov: 32)

Consequence

FAT1
NM_005245.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.620

Publications

4 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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 4-186595501-T-A is Benign according to our data. Variant chr4-186595501-T-A is described in CliVar as Benign. Clinvar id is 1272616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186595501-T-A is described in CliVar as Benign. Clinvar id is 1272616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186595501-T-A is described in CliVar as Benign. Clinvar id is 1272616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186595501-T-A is described in CliVar as Benign. Clinvar id is 1272616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186595501-T-A is described in CliVar as Benign. Clinvar id is 1272616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186595501-T-A is described in CliVar as Benign. Clinvar id is 1272616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186595501-T-A is described in CliVar as Benign. Clinvar id is 1272616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186595501-T-A is described in CliVar as Benign. Clinvar id is 1272616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186595501-T-A is described in CliVar as Benign. Clinvar id is 1272616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186595501-T-A is described in CliVar as Benign. Clinvar id is 1272616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-186595501-T-A is described in CliVar as Benign. Clinvar id is 1272616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FAT1	NM_005245.4 link	c.13138+188A>T	intron_variant	Intron 26 of 26	ENST00000441802.7	NP_005236.2	Q14517
FAT1	NM_001440456.1 link	c.13138+188A>T	intron_variant	Intron 26 of 27		NP_001427385.1
FAT1	NM_001440457.1 link	c.13138+188A>T	intron_variant	Intron 26 of 27		NP_001427386.1
FAT1	NM_001440455.1 link	c.13138+188A>T	intron_variant	Intron 26 of 26		NP_001427384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT1	ENST00000441802.7 link	c.13138+188A>T		intron_variant	Intron 26 of 26	5	NM_005245.4	ENSP00000406229.2		Q14517

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45605

AN:

151950

Hom.:

7163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.377

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.324

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.300

AC:

45612

AN:

152068

Hom.:

7167

Cov.:

AF XY:

0.300

AC XY:

22338

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.234

AC:

9690

AN:

41490

American (AMR)

AF:

0.377

AC:

5763

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.424

AC:

1472

AN:

3468

East Asian (EAS)

AF:

0.395

AC:

2038

AN:

5164

South Asian (SAS)

AF:

0.234

AC:

1123

AN:

4806

European-Finnish (FIN)

AF:

0.286

AC:

3020

AN:

10576

Middle Eastern (MID)

AF:

0.401

AC:

118

AN:

294

European-Non Finnish (NFE)

AF:

0.316

AC:

21467

AN:

67964

Other (OTH)

AF:

0.324

AC:

684

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1630

3260

4890

6520

8150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.135

Hom.:

248

Bravo

AF:

0.306

Asia WGS

AF:

0.283

AC:

987

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.19

(source)

DANN

Benign

0.52

PhyloP100

-0.62

PromoterAI

-0.014

Neutral

(source)

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over