4-186665056-C-T

Variant names:

• chr4-186665056-C-T
• rs2130910
• NM_005245.4:c.3266-1443G>A

Variant summary

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

The NM_005245.4(FAT1):​c.3266-1443G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,986 control chromosomes in the GnomAD database, including 24,953 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 0.57 (24953 hom., cov: 32)
• Consequence: FAT1 NM_005245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 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.3266-1443G>A		intron	N/A	NP_005236.2
	FAT1	NM_001440456.1		c.3266-1443G>A		intron	N/A	NP_001427385.1
	FAT1	NM_001440457.1		c.3266-1443G>A		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.3266-1443G>A		intron	N/A	ENSP00000406229.2
	FAT1	ENST00000917425.1		c.3266-1443G>A		intron	N/A	ENSP00000587484.1
	FAT1	ENST00000917424.1		c.3266-1443G>A		intron	N/A	ENSP00000587483.1

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86455 AN: 151868 Hom.: 24919 Cov.: 32

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.569 AC: 86546 AN: 151986 Hom.: 24953 Cov.: 32 AF XY: 0.570 AC XY: 42302 AN XY: 74262

African (AFR) AF: 0.670 AC: 27760 AN: 41456

American (AMR) AF: 0.623 AC: 9519 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 1955 AN: 3466

East Asian (EAS) AF: 0.651 AC: 3367 AN: 5172

South Asian (SAS) AF: 0.444 AC: 2138 AN: 4812

European-Finnish (FIN) AF: 0.490 AC: 5152 AN: 10518

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.513 AC: 34835 AN: 67962

Other (OTH) AF: 0.585 AC: 1235 AN: 2112

Alfa AF: 0.538 Hom.: 67431

Bravo AF: 0.588

Asia WGS AF: 0.570 AC: 1982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.16
PhyloP100		-0.47
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: rs2130910; hg19: chr4-187586210;