rs1280100

chr4-186616979-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005245.4(FAT1):c.9075+26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 1,585,358 control chromosomes in the GnomAD database, including 279,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (33468 hom., cov: 33)
  • Exomes 𝑓: 0.58 (246123 hom.)
• Consequence: FAT1 NM_005245.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.179

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-186616979-A-G is Benign according to our data. Variant chr4-186616979-A-G is described in ClinVar as [Benign]. Clinvar id is 1271179.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAT1	NM_005245.4	c.9075+26T>C		intron_variant		ENST00000441802.7
FAT1	XM_005262834.4	c.9075+26T>C		intron_variant
FAT1	XM_005262835.3	c.9075+26T>C		intron_variant
FAT1	XM_006714139.4	c.9075+26T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAT1	ENST00000441802.7	c.9075+26T>C		intron_variant		5	NM_005245.4	P1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99465 AN: 151966 Hom.: 33413 Cov.: 33

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.636

GnomAD3 exomes AF: 0.605 AC: 141144 AN: 233460 Hom.: 43844 AF XY: 0.592 AC XY: 74962 AN XY: 126564

Gnomad AFR exome AF: 0.828

Gnomad AMR exome AF: 0.688

Gnomad ASJ exome AF: 0.627

Gnomad EAS exome AF: 0.679

Gnomad SAS exome AF: 0.450

Gnomad FIN exome AF: 0.594

Gnomad NFE exome AF: 0.576

Gnomad OTH exome AF: 0.596

GnomAD4 exome AF: 0.583 AC: 835478 AN: 1433274 Hom.: 246123 Cov.: 25 AF XY: 0.578 AC XY: 411839 AN XY: 712268

Gnomad4 AFR exome AF: 0.831

Gnomad4 AMR exome AF: 0.682

Gnomad4 ASJ exome AF: 0.621

Gnomad4 EAS exome AF: 0.690

Gnomad4 SAS exome AF: 0.455

Gnomad4 FIN exome AF: 0.588

Gnomad4 NFE exome AF: 0.576

Gnomad4 OTH exome AF: 0.596

GnomAD4 genome AF: 0.655 AC: 99585 AN: 152084 Hom.: 33468 Cov.: 33 AF XY: 0.654 AC XY: 48641 AN XY: 74358

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.634

Alfa AF: 0.594 Hom.: 14021

Bravo AF: 0.673

Asia WGS AF: 0.583 AC: 2033 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	0.40
Dann	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1280100; hg19: chr4-187538133; COSMIC: COSV71672985;