Variant 4-186588338-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005245.4(FAT1):c.*254G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 460,638 control chromosomes in the GnomAD database, including 323 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 205 hom., cov: 32)

Exomes 𝑓: 0.014 ( 118 hom. )

Consequence

FAT1
NM_005245.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0600

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 4-186588338-C-T is Benign according to our data. Variant chr4-186588338-C-T is described in ClinVar as [Benign]. Clinvar id is 1274388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
FAT1	NM_005245.4 linkuse as main transcript	c.*254G>A	3_prime_UTR_variant	27/27	ENST00000441802.7
FAT1	XM_005262834.4 linkuse as main transcript	c.*254G>A	3_prime_UTR_variant	28/28
FAT1	XM_005262835.3 linkuse as main transcript	c.*254G>A	3_prime_UTR_variant	28/28
FAT1	XM_006714139.4 linkuse as main transcript	c.*254G>A	3_prime_UTR_variant	27/27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAT1	ENST00000441802.7 linkuse as main transcript	c.*254G>A		3_prime_UTR_variant	27/27	5	NM_005245.4	P1
FAT1	ENST00000500085.2 linkuse as main transcript	n.1713G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0325

AC:

4938

AN:

152020

Hom.:

204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0949

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0190

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.0428

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.00378

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00462

Gnomad OTH

AF:

0.0250

GnomAD4 exome

AF:

0.0135

AC:

4169

AN:

308498

Hom.:

118

Cov.:

AF XY:

0.0125

AC XY:

1962

AN XY:

157244

show subpopulations

Gnomad4 AFR exome

AF:

0.0954

Gnomad4 AMR exome

AF:

0.0140

Gnomad4 ASJ exome

AF:

0.0152

Gnomad4 EAS exome

AF:

0.0639

Gnomad4 SAS exome

AF:

0.00469

Gnomad4 FIN exome

AF:

0.00303

Gnomad4 NFE exome

AF:

0.00412

Gnomad4 OTH exome

AF:

0.0150

GnomAD4 genome

AF:

0.0325

AC:

4944

AN:

152140

Hom.:

205

Cov.:

AF XY:

0.0315

AC XY:

2343

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0948

Gnomad4 AMR

AF:

0.0190

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.0429

Gnomad4 SAS

AF:

0.00704

Gnomad4 FIN

AF:

0.00378

Gnomad4 NFE

AF:

0.00462

Gnomad4 OTH

AF:

0.0247

Alfa

AF:

0.0135

Hom.:

Bravo

AF:

0.0367

Asia WGS

AF:

0.0290

AC:

103

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 03, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.24

DANN

Benign

0.64

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