4-186680808-T-C

Variant names:

• chr4-186680808-T-C
• rs455600
• NM_005245.4:c.3266-17195A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005245.4(FAT1):​c.3266-17195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,094 control chromosomes in the GnomAD database, including 49,922 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.80 (49922 hom., cov: 32)
• Consequence: FAT1 NM_005245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis

  Inheritance: AR Classification: STRONG Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.893 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005245.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAT1	NM_005245.4	MANE Select	c.3266-17195A>G		intron	N/A	NP_005236.2	Q14517
	FAT1	NM_001440456.1		c.3266-17195A>G		intron	N/A	NP_001427385.1
	FAT1	NM_001440457.1		c.3266-17195A>G		intron	N/A	NP_001427386.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAT1	ENST00000441802.7	TSL:5 MANE Select	c.3266-17195A>G		intron	N/A	ENSP00000406229.2	Q14517
	FAT1	ENST00000917425.1		c.3266-17195A>G		intron	N/A	ENSP00000587484.1
	FAT1	ENST00000917424.1		c.3266-17195A>G		intron	N/A	ENSP00000587483.1

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121839 AN: 151974 Hom.: 49858 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.799

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.802 AC: 121966 AN: 152094 Hom.: 49922 Cov.: 32 AF XY: 0.793 AC XY: 58965 AN XY: 74358

African (AFR) AF: 0.900 AC: 37395 AN: 41536

American (AMR) AF: 0.671 AC: 10245 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3016 AN: 3470

East Asian (EAS) AF: 0.372 AC: 1914 AN: 5148

South Asian (SAS) AF: 0.801 AC: 3860 AN: 4816

European-Finnish (FIN) AF: 0.695 AC: 7335 AN: 10552

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55498 AN: 67986

Other (OTH) AF: 0.798 AC: 1684 AN: 2110

Alfa AF: 0.804 Hom.: 148318

Bravo AF: 0.796

Asia WGS AF: 0.604 AC: 2103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.58
DANN	Benign	0.27
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs455600; hg19: chr4-187601962;