rs6553016

Variant names:

• chr4-186655947-C-T
• rs6553016
• NM_005245.4:c.3580+7352G>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.3580+7352G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,196 control chromosomes in the GnomAD database, including 10,286 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 0.36 (10286 hom., cov: 33)
• Consequence: FAT1 NM_005245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT1	NM_005245.4	c.3580+7352G>A		intron_variant	Intron 3 of 26	ENST00000441802.7	NP_005236.2
FAT1	NM_001440456.1	c.3580+7352G>A		intron_variant	Intron 3 of 27		NP_001427385.1
FAT1	NM_001440457.1	c.3580+7352G>A		intron_variant	Intron 3 of 27		NP_001427386.1
FAT1	NM_001440455.1	c.3580+7352G>A		intron_variant	Intron 3 of 26		NP_001427384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT1	ENST00000441802.7	c.3580+7352G>A		intron_variant	Intron 3 of 26	5	NM_005245.4	ENSP00000406229.2

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54910 AN: 152078 Hom.: 10277 Cov.: 33

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.0534

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.361 AC: 54955 AN: 152196 Hom.: 10286 Cov.: 33 AF XY: 0.356 AC XY: 26467 AN XY: 74402

African (AFR) AF: 0.368 AC: 15289 AN: 41530

American (AMR) AF: 0.306 AC: 4681 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1630 AN: 3466

East Asian (EAS) AF: 0.0533 AC: 276 AN: 5178

South Asian (SAS) AF: 0.315 AC: 1517 AN: 4822

European-Finnish (FIN) AF: 0.329 AC: 3476 AN: 10580

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26761 AN: 68004

Other (OTH) AF: 0.401 AC: 847 AN: 2114

Alfa AF: 0.384 Hom.: 5943

Bravo AF: 0.355

Asia WGS AF: 0.198 AC: 691 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	0.72
DANN	Benign	0.66
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6553016; hg19: chr4-187577101;