rs10008621

chr4-186629543-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005245.4(FAT1):c.4324-780G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,210 control chromosomes in the GnomAD database, including 1,617 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 0.14 (1617 hom., cov: 32)
• Consequence: FAT1 NM_005245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAT1	NM_005245.4	c.4324-780G>A		intron_variant		ENST00000441802.7
FAT1	XM_005262834.4	c.4324-780G>A		intron_variant
FAT1	XM_005262835.3	c.4324-780G>A		intron_variant
FAT1	XM_006714139.4	c.4324-780G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAT1	ENST00000441802.7	c.4324-780G>A		intron_variant		5	NM_005245.4	P1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20989 AN: 152092 Hom.: 1613 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.138 AC: 21000 AN: 152210 Hom.: 1617 Cov.: 32 AF XY: 0.142 AC XY: 10546 AN XY: 74408

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.139

Alfa AF: 0.125 Hom.: 1612

Bravo AF: 0.137

Asia WGS AF: 0.199 AC: 693 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	1.5
Dann	Benign	0.65

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: rs10008621; hg19: chr4-187550697;