rs1014867

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001291303.3(FAT4):c.14920C>T(p.Pro4974Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0542 in 1,613,234 control chromosomes in the GnomAD database, including 2,483 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 205 hom., cov: 33)

Exomes 𝑓: 0.055 ( 2278 hom. )

Consequence

FAT4
NM_001291303.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.697

Variant links:

Genes affected

FAT4 (HGNC:23109): (FAT atypical cadherin 4) The protein encoded by this gene is a member of the protocadherin family. This gene may play a role in regulating planar cell polarity (PCP). Studies in mice suggest that loss of PCP signaling may cause cystic kidney disease, and mutations in this gene have been associated with Van Maldergem Syndrome 2. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Mar 2014]

FAT4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019827187).

BP6

Variant 4-125491736-C-T is Benign according to our data. Variant chr4-125491736-C-T is described in ClinVar as [Benign]. Clinvar id is 380911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-125491736-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT4	NM_001291303.3 link	c.14920C>T	p.Pro4974Ser	missense_variant	Exon 18 of 18	ENST00000394329.9	NP_001278232.1	Q6V0I7A0A6Q8JR05X2G5I7B3KU84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FAT4	ENST00000394329.9 link	c.14920C>T	p.Pro4974Ser	missense_variant	Exon 18 of 18	5	NM_001291303.3	ENSP00000377862.4	A0A6Q8JR05
FAT4	ENST00000335110.5 link	c.9637C>T	p.Pro3213Ser	missense_variant	Exon 15 of 15	1		ENSP00000335169.5	Q6V0I7-2
FAT4	ENST00000674496.2 link	c.9691C>T	p.Pro3231Ser	missense_variant	Exon 17 of 17			ENSP00000501473.2	A0A7P0T1I0

Frequencies

GnomAD3 genomes

AF:

0.0493

AC:

7501

AN:

152128

Hom.:

203

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0507

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0345

Gnomad ASJ

AF:

0.0138

Gnomad EAS

AF:

0.0629

Gnomad SAS

AF:

0.0352

Gnomad FIN

AF:

0.0336

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0569

Gnomad OTH

AF:

0.0455

GnomAD3 exomes

AF:

0.0486

AC:

12139

AN:

249872

Hom.:

336

AF XY:

0.0486

AC XY:

6570

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.0523

Gnomad AMR exome

AF:

0.0344

Gnomad ASJ exome

AF:

0.0163

Gnomad EAS exome

AF:

0.0557

Gnomad SAS exome

AF:

0.0399

Gnomad FIN exome

AF:

0.0394

Gnomad NFE exome

AF:

0.0579

Gnomad OTH exome

AF:

0.0533

GnomAD4 exome

AF:

0.0547

AC:

79848

AN:

1460988

Hom.:

2278

Cov.:

AF XY:

0.0540

AC XY:

39230

AN XY:

726766

show subpopulations

Gnomad4 AFR exome

AF:

0.0526

Gnomad4 AMR exome

AF:

0.0345

Gnomad4 ASJ exome

AF:

0.0175

Gnomad4 EAS exome

AF:

0.0585

Gnomad4 SAS exome

AF:

0.0386

Gnomad4 FIN exome

AF:

0.0413

Gnomad4 NFE exome

AF:

0.0583

Gnomad4 OTH exome

AF:

0.0517

GnomAD4 genome

AF:

0.0493

AC:

7511

AN:

152246

Hom.:

205

Cov.:

AF XY:

0.0469

AC XY:

3493

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0508

Gnomad4 AMR

AF:

0.0343

Gnomad4 ASJ

AF:

0.0138

Gnomad4 EAS

AF:

0.0628

Gnomad4 SAS

AF:

0.0350

Gnomad4 FIN

AF:

0.0336

Gnomad4 NFE

AF:

0.0569

Gnomad4 OTH

AF:

0.0459

Alfa

AF:

0.0536

Hom.:

527

Bravo

AF:

0.0495

TwinsUK

AF:

0.0537

AC:

199

ALSPAC

AF:

0.0511

AC:

197

ESP6500AA

AF:

0.0497

AC:

219

ESP6500EA

AF:

0.0527

AC:

453

ExAC

AF:

0.0503

AC:

6107

Asia WGS

AF:

0.0560

AC:

194

AN:

3478

EpiCase

AF:

0.0517

EpiControl

AF:

0.0518

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 04, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.2

DANN

Benign

0.67

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.11

N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.053

Sift

Benign

0.35

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.0

B;B

Vest4

0.046

MPC

0.15

ClinPred

0.0016

GERP RS

2.8

Varity_R

0.021

gMVP

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over