4-186595501-T-C

Variant names:

• chr4-186595501-T-C
• rs2306987
• NM_005245.4:c.13138+188A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005245.4(FAT1):​c.13138+188A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: FAT1 NM_005245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT1	NM_005245.4	c.13138+188A>G		intron_variant	Intron 26 of 26	ENST00000441802.7	NP_005236.2
FAT1	NM_001440456.1	c.13138+188A>G		intron_variant	Intron 26 of 27		NP_001427385.1
FAT1	NM_001440457.1	c.13138+188A>G		intron_variant	Intron 26 of 27		NP_001427386.1
FAT1	NM_001440455.1	c.13138+188A>G		intron_variant	Intron 26 of 26		NP_001427384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT1	ENST00000441802.7	c.13138+188A>G		intron_variant	Intron 26 of 26	5	NM_005245.4	ENSP00000406229.2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.23
DANN	Benign	0.44
PhyloP100		-0.62
PromoterAI		-0.0028	Neutral

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: rs2306987; hg19: chr4-187516655;