chr4-186700910-A-G

Variant names:

• chr4-186700910-A-G
• rs455219
• NM_005245.4:c.3265+5653T>C

Variant summary

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

The NM_005245.4(FAT1):​c.3265+5653T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,966 control chromosomes in the GnomAD database, including 10,334 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 0.33 (10334 hom., cov: 32)
• Consequence: FAT1 NM_005245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 7 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT1	NM_005245.4	c.3265+5653T>C		intron_variant	Intron 2 of 26	ENST00000441802.7	NP_005236.2
FAT1	NM_001440456.1	c.3265+5653T>C		intron_variant	Intron 2 of 27		NP_001427385.1
FAT1	NM_001440457.1	c.3265+5653T>C		intron_variant	Intron 2 of 27		NP_001427386.1
FAT1	NM_001440455.1	c.3265+5653T>C		intron_variant	Intron 2 of 26		NP_001427384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT1	ENST00000441802.7	c.3265+5653T>C		intron_variant	Intron 2 of 26	5	NM_005245.4	ENSP00000406229.2

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50516 AN: 151848 Hom.: 10307 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.333 AC: 50590 AN: 151966 Hom.: 10334 Cov.: 32 AF XY: 0.335 AC XY: 24910 AN XY: 74288

African (AFR) AF: 0.578 AC: 23928 AN: 41424

American (AMR) AF: 0.257 AC: 3926 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3470

East Asian (EAS) AF: 0.361 AC: 1852 AN: 5132

South Asian (SAS) AF: 0.339 AC: 1634 AN: 4818

European-Finnish (FIN) AF: 0.249 AC: 2638 AN: 10588

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14893 AN: 67944

Other (OTH) AF: 0.309 AC: 651 AN: 2106

Alfa AF: 0.250 Hom.: 23449

Bravo AF: 0.339

Asia WGS AF: 0.387 AC: 1347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.37
PhyloP100		-0.059
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs455219; hg19: chr4-187622064;