rs1014866

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001291303.3(FAT4):c.14604A>G(p.Arg4868Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 1,613,936 control chromosomes in the GnomAD database, including 469,456 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 42823 hom., cov: 32)

Exomes 𝑓: 0.76 ( 426633 hom. )

Consequence

FAT4
NM_001291303.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.917

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 4-125491420-A-G is Benign according to our data. Variant chr4-125491420-A-G is described in ClinVar as [Benign]. Clinvar id is 380802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-125491420-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.917 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAT4	NM_001291303.3 linkuse as main transcript	c.14604A>G	p.Arg4868Arg	synonymous_variant	18/18	ENST00000394329.9	NP_001278232.1	Q6V0I7A0A6Q8JR05X2G5I7B3KU84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FAT4	ENST00000394329.9 linkuse as main transcript	c.14604A>G	p.Arg4868Arg	synonymous_variant	18/18	5	NM_001291303.3	ENSP00000377862.4	A0A6Q8JR05
FAT4	ENST00000335110.5 linkuse as main transcript	c.9321A>G	p.Arg3107Arg	synonymous_variant	15/15	1		ENSP00000335169.5	Q6V0I7-2
FAT4	ENST00000674496.2 linkuse as main transcript	c.9375A>G	p.Arg3125Arg	synonymous_variant	17/17			ENSP00000501473.2	A0A7P0T1I0

Frequencies

GnomAD3 genomes

AF:

0.748

AC:

113755

AN:

151978

Hom.:

42778

Cov.:

show subpopulations

Gnomad AFR

AF:

0.698

Gnomad AMI

AF:

0.912

Gnomad AMR

AF:

0.737

Gnomad ASJ

AF:

0.771

Gnomad EAS

AF:

0.855

Gnomad SAS

AF:

0.746

Gnomad FIN

AF:

0.793

Gnomad MID

AF:

0.775

Gnomad NFE

AF:

0.763

Gnomad OTH

AF:

0.753

GnomAD3 exomes

AF:

0.758

AC:

190405

AN:

251236

Hom.:

72482

AF XY:

0.759

AC XY:

103063

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.692

Gnomad AMR exome

AF:

0.716

Gnomad ASJ exome

AF:

0.764

Gnomad EAS exome

AF:

0.874

Gnomad SAS exome

AF:

0.733

Gnomad FIN exome

AF:

0.797

Gnomad NFE exome

AF:

0.759

Gnomad OTH exome

AF:

0.764

GnomAD4 exome

AF:

0.763

AC:

1115791

AN:

1461840

Hom.:

426633

Cov.:

AF XY:

0.763

AC XY:

554791

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.693

Gnomad4 AMR exome

AF:

0.719

Gnomad4 ASJ exome

AF:

0.773

Gnomad4 EAS exome

AF:

0.864

Gnomad4 SAS exome

AF:

0.734

Gnomad4 FIN exome

AF:

0.795

Gnomad4 NFE exome

AF:

0.764

Gnomad4 OTH exome

AF:

0.763

GnomAD4 genome

AF:

0.749

AC:

113858

AN:

152096

Hom.:

42823

Cov.:

AF XY:

0.750

AC XY:

55753

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.698

Gnomad4 AMR

AF:

0.738

Gnomad4 ASJ

AF:

0.771

Gnomad4 EAS

AF:

0.855

Gnomad4 SAS

AF:

0.746

Gnomad4 FIN

AF:

0.793

Gnomad4 NFE

AF:

0.763

Gnomad4 OTH

AF:

0.755

Alfa

AF:

0.756

Hom.:

73423

Bravo

AF:

0.742

Asia WGS

AF:

0.796

AC:

2766

AN:

3478

EpiCase

AF:

0.762

EpiControl

AF:

0.760

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 91% of patients studied by a panel of primary immunodeficiencies. Number of patients: 86. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 76% of total chromosomes in ExAC -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 08, 2016	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. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Van Maldergem syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Hennekam lymphangiectasia-lymphedema syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.3

DANN

Benign

0.69

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