Variant 4-186588460-G-A 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.*132C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 1,086,018 control chromosomes in the GnomAD database, including 1,483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 228 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1255 hom. )

Consequence

FAT1
NM_005245.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.90

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=-0.85).

BP6

Variant 4-186588460-G-A is Benign according to our data. Variant chr4-186588460-G-A is described in ClinVar as [Benign]. Clinvar id is 1257852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
FAT1	NM_005245.4 linkuse as main transcript	c.*132C>T	3_prime_UTR_variant	27/27	ENST00000441802.7
FAT1	XM_005262834.4 linkuse as main transcript	c.*132C>T	3_prime_UTR_variant	28/28
FAT1	XM_005262835.3 linkuse as main transcript	c.*132C>T	3_prime_UTR_variant	28/28
FAT1	XM_006714139.4 linkuse as main transcript	c.*132C>T	3_prime_UTR_variant	27/27

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
FAT1	ENST00000441802.7 linkuse as main transcript	c.*132C>T	3_prime_UTR_variant	27/27	5	NM_005245.4	P1
FAT1	ENST00000512772.5 linkuse as main transcript	c.*132C>T	3_prime_UTR_variant	4/4	2
FAT1	ENST00000500085.2 linkuse as main transcript	n.1591C>T	non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0367

AC:

5589

AN:

152124

Hom.:

223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00862

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0836

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.174

Gnomad SAS

AF:

0.0132

Gnomad FIN

AF:

0.0798

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0298

Gnomad OTH

AF:

0.0273

GnomAD4 exome

AF:

0.0385

AC:

35927

AN:

933774

Hom.:

1255

Cov.:

AF XY:

0.0373

AC XY:

17327

AN XY:

463926

show subpopulations

Gnomad4 AFR exome

AF:

0.00505

Gnomad4 AMR exome

AF:

0.120

Gnomad4 ASJ exome

AF:

0.00618

Gnomad4 EAS exome

AF:

0.183

Gnomad4 SAS exome

AF:

0.0121

Gnomad4 FIN exome

AF:

0.0687

Gnomad4 NFE exome

AF:

0.0321

Gnomad4 OTH exome

AF:

0.0379

GnomAD4 genome

AF:

0.0368

AC:

5600

AN:

152244

Hom.:

228

Cov.:

AF XY:

0.0399

AC XY:

2972

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00859

Gnomad4 AMR

AF:

0.0845

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.175

Gnomad4 SAS

AF:

0.0132

Gnomad4 FIN

AF:

0.0798

Gnomad4 NFE

AF:

0.0298

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.0329

Hom.:

Bravo

AF:

0.0407

Asia WGS

AF:

0.0950

AC:

330

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.5

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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