rs2940779

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.2944T>C(p.Leu982Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 1,612,446 control chromosomes in the GnomAD database, including 405,804 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42865 hom., cov: 32)

Exomes 𝑓: 0.70 ( 362939 hom. )

Consequence

FAT4
NM_001291303.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.103

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:

FAT4 (HGNC:):

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=-0.76).

BP6

Variant 4-125319355-T-C is Benign according to our data. Variant chr4-125319355-T-C is described in ClinVar as [Benign]. Clinvar id is 380793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-125319355-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.103 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 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.2944T>C	p.Leu982Leu	synonymous_variant	2/18	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.2944T>C	p.Leu982Leu	synonymous_variant	2/18	5	NM_001291303.3	ENSP00000377862.4	A0A6Q8JR05
FAT4	ENST00000674496.2 linkuse as main transcript	c.-55+3378T>C		intron_variant				ENSP00000501473.2	A0A7P0T1I0
FAT4	ENST00000678072.1 linkuse as main transcript	n.550T>C		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

AF:

0.743

AC:

112857

AN:

151974

Hom.:

42797

Cov.:

show subpopulations

Gnomad AFR

AF:

0.885

Gnomad AMI

AF:

0.698

Gnomad AMR

AF:

0.731

Gnomad ASJ

AF:

0.731

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.727

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.708

Gnomad OTH

AF:

0.737

GnomAD3 exomes

AF:

0.694

AC:

172971

AN:

249100

Hom.:

61069

AF XY:

0.695

AC XY:

94002

AN XY:

135190

show subpopulations

Gnomad AFR exome

AF:

0.890

Gnomad AMR exome

AF:

0.699

Gnomad ASJ exome

AF:

0.731

Gnomad EAS exome

AF:

0.470

Gnomad SAS exome

AF:

0.752

Gnomad FIN exome

AF:

0.576

Gnomad NFE exome

AF:

0.705

Gnomad OTH exome

AF:

0.690

GnomAD4 exome

AF:

0.703

AC:

1026299

AN:

1460354

Hom.:

362939

Cov.:

AF XY:

0.704

AC XY:

511406

AN XY:

726632

show subpopulations

Gnomad4 AFR exome

AF:

0.897

Gnomad4 AMR exome

AF:

0.703

Gnomad4 ASJ exome

AF:

0.735

Gnomad4 EAS exome

AF:

0.486

Gnomad4 SAS exome

AF:

0.747

Gnomad4 FIN exome

AF:

0.581

Gnomad4 NFE exome

AF:

0.706

Gnomad4 OTH exome

AF:

0.705

GnomAD4 genome

AF:

0.743

AC:

112984

AN:

152092

Hom.:

42865

Cov.:

AF XY:

0.735

AC XY:

54599

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.886

Gnomad4 AMR

AF:

0.731

Gnomad4 ASJ

AF:

0.731

Gnomad4 EAS

AF:

0.473

Gnomad4 SAS

AF:

0.727

Gnomad4 FIN

AF:

0.573

Gnomad4 NFE

AF:

0.708

Gnomad4 OTH

AF:

0.740

Alfa

AF:

0.711

Hom.:

87536

Bravo

AF:

0.755

Asia WGS

AF:

0.670

AC:

2332

AN:

3478

EpiCase

AF:

0.706

EpiControl

AF:

0.706

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
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: 70% 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, 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 95% of patients studied by a panel of primary immunodeficiencies. Number of patients: 90. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

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

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

-0.76

CADD

Benign

3.1

DANN

Benign

0.65

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