4-186680808-T-C

Position:

• chr4-186680808-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAT1	NM_005245.4	c.3266-17195A>G		intron_variant		ENST00000441802.7	NP_005236.2
FAT1	XM_005262834.4	c.3266-17195A>G		intron_variant			XP_005262891.1
FAT1	XM_005262835.3	c.3266-17195A>G		intron_variant			XP_005262892.1
FAT1	XM_006714139.4	c.3266-17195A>G		intron_variant			XP_006714202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAT1	ENST00000441802.7	c.3266-17195A>G		intron_variant		5	NM_005245.4	ENSP00000406229	P1

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

Gnomad4 AFR AF: 0.900

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.869

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.801

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.798

Alfa AF: 0.806 Hom.: 98518

Bravo AF: 0.796

Asia WGS AF: 0.604 AC: 2103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.58
DANN	Benign	0.27

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: rs455600; hg19: chr4-187601962;