rs10008621

Variant names:

• chr4-186629543-C-T
• rs10008621
• NM_005245.4:c.4324-780G>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.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
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.325 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAT1	NM_005245.4	MANE Select	c.4324-780G>A		intron	N/A	NP_005236.2
	FAT1	NM_001440456.1		c.4324-780G>A		intron	N/A	NP_001427385.1
	FAT1	NM_001440457.1		c.4324-780G>A		intron	N/A	NP_001427386.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAT1	ENST00000441802.7	TSL:5 MANE Select	c.4324-780G>A		intron	N/A	ENSP00000406229.2

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

African (AFR) AF: 0.124 AC: 5156 AN: 41532

American (AMR) AF: 0.170 AC: 2601 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 512 AN: 3470

East Asian (EAS) AF: 0.338 AC: 1751 AN: 5182

South Asian (SAS) AF: 0.106 AC: 512 AN: 4822

European-Finnish (FIN) AF: 0.142 AC: 1500 AN: 10576

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8532 AN: 68004

Other (OTH) AF: 0.139 AC: 293 AN: 2114

Alfa AF: 0.126 Hom.: 2060

Bravo AF: 0.137

Asia WGS AF: 0.199 AC: 693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.65
PhyloP100		-0.51
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: rs10008621; hg19: chr4-187550697;