Variant 4-186597822-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005245.4(FAT1):c.12258-30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,591,240 control chromosomes in the GnomAD database, including 99,153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.32 ( 8715 hom., cov: 32)

Exomes 𝑓: 0.35 ( 90438 hom. )

Consequence

FAT1
NM_005245.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.538

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 4-186597822-C-T is Benign according to our data. Variant chr4-186597822-C-T is described in ClinVar as [Benign]. Clinvar id is 1261827.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
FAT1	NM_005245.4 linkuse as main transcript	c.12258-30G>A	intron_variant	ENST00000441802.7
FAT1	XM_005262834.4 linkuse as main transcript	c.12258-30G>A	intron_variant
FAT1	XM_005262835.3 linkuse as main transcript	c.12258-30G>A	intron_variant
FAT1	XM_006714139.4 linkuse as main transcript	c.12258-30G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
FAT1	ENST00000441802.7 linkuse as main transcript	c.12258-30G>A	intron_variant	5	NM_005245.4	P1
FAT1	ENST00000507105.1 linkuse as main transcript	c.54-30G>A	intron_variant	3
FAT1	ENST00000507662.1 linkuse as main transcript	n.157-30G>A	intron_variant, non_coding_transcript_variant	5
FAT1	ENST00000512347.1 linkuse as main transcript	n.450-30G>A	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48760

AN:

151824

Hom.:

8707

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.456

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.567

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.382

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.341

GnomAD3 exomes

AF:

0.374

AC:

91479

AN:

244414

Hom.:

18685

AF XY:

0.364

AC XY:

48280

AN XY:

132562

show subpopulations

Gnomad AFR exome

AF:

0.176

Gnomad AMR exome

AF:

0.550

Gnomad ASJ exome

AF:

0.389

Gnomad EAS exome

AF:

0.580

Gnomad SAS exome

AF:

0.247

Gnomad FIN exome

AF:

0.383

Gnomad NFE exome

AF:

0.347

Gnomad OTH exome

AF:

0.371

GnomAD4 exome

AF:

0.347

AC:

499198

AN:

1439298

Hom.:

90438

Cov.:

AF XY:

0.344

AC XY:

246383

AN XY:

717046

show subpopulations

Gnomad4 AFR exome

AF:

0.170

Gnomad4 AMR exome

AF:

0.535

Gnomad4 ASJ exome

AF:

0.387

Gnomad4 EAS exome

AF:

0.586

Gnomad4 SAS exome

AF:

0.248

Gnomad4 FIN exome

AF:

0.379

Gnomad4 NFE exome

AF:

0.341

Gnomad4 OTH exome

AF:

0.342

GnomAD4 genome

AF:

0.321

AC:

48774

AN:

151942

Hom.:

8715

Cov.:

AF XY:

0.326

AC XY:

24192

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.457

Gnomad4 ASJ

AF:

0.389

Gnomad4 EAS

AF:

0.567

Gnomad4 SAS

AF:

0.249

Gnomad4 FIN

AF:

0.385

Gnomad4 NFE

AF:

0.347

Gnomad4 OTH

AF:

0.340

Alfa

AF:

0.346

Hom.:

9380

Bravo

AF:

0.327

Asia WGS

AF:

0.388

AC:

1348

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.6

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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