dbSNP rs1298865: FAT1:p.Ser4367Ser (chr4-186595726-A-G) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005245.4(FAT1):c.13101T>C(p.Ser4367Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,613,448 control chromosomes in the GnomAD database, including 128,044 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 18538 hom., cov: 32)

Exomes 𝑓: 0.38 ( 109506 hom. )

Consequence

FAT1
NM_005245.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.424

Publications

23 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.121).

BP6

Variant 4-186595726-A-G is Benign according to our data. Variant chr4-186595726-A-G is described in ClinVar as Benign. ClinVar VariationId is 1273862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.424 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

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
FAT1	NM_005245.4	MANE Select	c.13101T>C	p.Ser4367Ser	synonymous	Exon 26 of 27	NP_005236.2
FAT1	NM_001440456.1		c.13101T>C	p.Ser4367Ser	synonymous	Exon 26 of 28	NP_001427385.1
FAT1	NM_001440457.1		c.13101T>C	p.Ser4367Ser	synonymous	Exon 26 of 28	NP_001427386.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FAT1	ENST00000441802.7	TSL:5 MANE Select	c.13101T>C	p.Ser4367Ser	synonymous	Exon 26 of 27	ENSP00000406229.2
FAT1	ENST00000509927.1	TSL:1	c.75T>C	p.Ser25Ser	synonymous	Exon 1 of 4	ENSP00000420869.1
FAT1	ENST00000512772.5	TSL:2	c.402T>C	p.Ser134Ser	synonymous	Exon 2 of 4	ENSP00000424157.1

Frequencies

GnomAD3 genomes

AF:

0.473

AC:

71923

AN:

151918

Hom.:

18513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.668

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.457

Gnomad EAS

AF:

0.609

Gnomad SAS

AF:

0.262

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.453

GnomAD2 exomes

AF:

0.426

AC:

106179

AN:

249204

AF XY:

0.408

show subpopulations

Gnomad AFR exome

AF:

0.675

Gnomad AMR exome

AF:

0.589

Gnomad ASJ exome

AF:

0.458

Gnomad EAS exome

AF:

0.621

Gnomad FIN exome

AF:

0.388

Gnomad NFE exome

AF:

0.362

Gnomad OTH exome

AF:

0.406

GnomAD4 exome

AF:

0.377

AC:

551315

AN:

1461412

Hom.:

109506

Cov.:

AF XY:

0.372

AC XY:

270371

AN XY:

727004

show subpopulations

African (AFR)

AF:

0.676

AC:

22637

AN:

33478

American (AMR)

AF:

0.578

AC:

25858

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.459

AC:

11995

AN:

26136

East Asian (EAS)

AF:

0.646

AC:

25659

AN:

39696

South Asian (SAS)

AF:

0.259

AC:

22332

AN:

86248

European-Finnish (FIN)

AF:

0.384

AC:

20522

AN:

53390

Middle Eastern (MID)

AF:

0.406

AC:

2340

AN:

5762

European-Non Finnish (NFE)

AF:

0.356

AC:

396081

AN:

1111630

Other (OTH)

AF:

0.396

AC:

23891

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

17299

34598

51897

69196

86495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12852

25704

38556

51408

64260

<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:

0.474

AC:

71998

AN:

152036

Hom.:

18538

Cov.:

AF XY:

0.475

AC XY:

35258

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.667

AC:

27669

AN:

41456

American (AMR)

AF:

0.526

AC:

8040

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.457

AC:

1587

AN:

3472

East Asian (EAS)

AF:

0.610

AC:

3139

AN:

5150

South Asian (SAS)

AF:

0.261

AC:

1259

AN:

4816

European-Finnish (FIN)

AF:

0.392

AC:

4149

AN:

10576

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.365

AC:

24791

AN:

67970

Other (OTH)

AF:

0.450

AC:

948

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1810

3620

5431

7241

9051

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.413

Hom.:

22147

Bravo

AF:

0.500

Asia WGS

AF:

0.445

AC:

1548

AN:

3478

EpiCase

AF:

0.362

EpiControl

AF:

0.362

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.3

(source)

DANN

Benign

0.61

PhyloP100

-0.42

PromoterAI

-0.0022

Neutral

(source)

Mutation Taster

=98/2

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over