rs2710555

Positions:

chr4-125320716-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001291303.3(FAT4):c.4305C>T(p.Ile1435Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 1,613,428 control chromosomes in the GnomAD database, including 403,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.73 ( 41728 hom., cov: 33)

Exomes 𝑓: 0.70 ( 361497 hom. )

Consequence

FAT4
NM_001291303.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.852

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 4-125320716-C-T is Benign according to our data. Variant chr4-125320716-C-T is described in ClinVar as [Benign]. Clinvar id is 377855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-125320716-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.852 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 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.4305C>T	p.Ile1435Ile	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.4305C>T	p.Ile1435Ile	synonymous_variant	2/18	5	NM_001291303.3	ENSP00000377862.4	A0A6Q8JR05
FAT4	ENST00000674496.2 linkuse as main transcript	c.-55+4739C>T		intron_variant				ENSP00000501473.2	A0A7P0T1I0
FAT4	ENST00000678072.1 linkuse as main transcript	n.1911C>T		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

AF:

0.734

AC:

111548

AN:

152058

Hom.:

41663

Cov.:

show subpopulations

Gnomad AFR

AF:

0.856

Gnomad AMI

AF:

0.696

Gnomad AMR

AF:

0.727

Gnomad ASJ

AF:

0.731

Gnomad EAS

AF:

0.462

Gnomad SAS

AF:

0.728

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.688

Gnomad NFE

AF:

0.707

Gnomad OTH

AF:

0.731

GnomAD3 exomes

AF:

0.691

AC:

172243

AN:

249316

Hom.:

60491

AF XY:

0.692

AC XY:

93656

AN XY:

135268

show subpopulations

Gnomad AFR exome

AF:

0.861

Gnomad AMR exome

AF:

0.697

Gnomad ASJ exome

AF:

0.731

Gnomad EAS exome

AF:

0.454

Gnomad SAS exome

AF:

0.751

Gnomad FIN exome

AF:

0.575

Gnomad NFE exome

AF:

0.705

Gnomad OTH exome

AF:

0.689

GnomAD4 exome

AF:

0.701

AC:

1024607

AN:

1461252

Hom.:

361497

Cov.:

AF XY:

0.702

AC XY:

510616

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.865

Gnomad4 AMR exome

AF:

0.700

Gnomad4 ASJ exome

AF:

0.735

Gnomad4 EAS exome

AF:

0.468

Gnomad4 SAS exome

AF:

0.747

Gnomad4 FIN exome

AF:

0.581

Gnomad4 NFE exome

AF:

0.706

Gnomad4 OTH exome

AF:

0.702

GnomAD4 genome

AF:

0.734

AC:

111672

AN:

152176

Hom.:

41728

Cov.:

AF XY:

0.726

AC XY:

53989

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.856

Gnomad4 AMR

AF:

0.726

Gnomad4 ASJ

AF:

0.731

Gnomad4 EAS

AF:

0.461

Gnomad4 SAS

AF:

0.729

Gnomad4 FIN

AF:

0.573

Gnomad4 NFE

AF:

0.707

Gnomad4 OTH

AF:

0.733

Alfa

AF:

0.718

Hom.:

53925

Bravo

AF:

0.744

Asia WGS

AF:

0.663

AC:

2309

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, 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	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, 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	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. -

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

-0.32

CADD

Benign

6.5

DANN

Benign

0.71

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