Variant 4-186595726-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005245.4(FAT1):c.13101T>C(p.Ser4367=) 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

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 4-186595726-A-G is Benign according to our data. Variant chr4-186595726-A-G is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FAT1	NM_005245.4 linkuse as main transcript	c.13101T>C	p.Ser4367=	synonymous_variant	26/27	ENST00000441802.7	NP_005236.2
FAT1	XM_005262834.4 linkuse as main transcript	c.13101T>C	p.Ser4367=	synonymous_variant	26/28		XP_005262891.1
FAT1	XM_005262835.3 linkuse as main transcript	c.13101T>C	p.Ser4367=	synonymous_variant	26/28		XP_005262892.1
FAT1	XM_006714139.4 linkuse as main transcript	c.13101T>C	p.Ser4367=	synonymous_variant	26/27		XP_006714202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAT1	ENST00000441802.7 linkuse as main transcript	c.13101T>C	p.Ser4367=	synonymous_variant	26/27	5	NM_005245.4	ENSP00000406229	P1

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

GnomAD3 exomes

AF:

0.426

AC:

106179

AN:

249204

Hom.:

24855

AF XY:

0.408

AC XY:

55114

AN XY:

135192

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 SAS exome

AF:

0.257

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

Gnomad4 AFR exome

AF:

0.676

Gnomad4 AMR exome

AF:

0.578

Gnomad4 ASJ exome

AF:

0.459

Gnomad4 EAS exome

AF:

0.646

Gnomad4 SAS exome

AF:

0.259

Gnomad4 FIN exome

AF:

0.384

Gnomad4 NFE exome

AF:

0.356

Gnomad4 OTH exome

AF:

0.396

GnomAD4 genome

AF:

0.474

AC:

71998

AN:

152036

Hom.:

18538

Cov.:

AF XY:

0.475

AC XY:

35258

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.667

Gnomad4 AMR

AF:

0.526

Gnomad4 ASJ

AF:

0.457

Gnomad4 EAS

AF:

0.610

Gnomad4 SAS

AF:

0.261

Gnomad4 FIN

AF:

0.392

Gnomad4 NFE

AF:

0.365

Gnomad4 OTH

AF:

0.450

Alfa

AF:

0.403

Hom.:

16883

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.3

DANN

Benign

0.61

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