NM_005245.4:c.3581-4219A>C

Variant names:

• chr4-186644002-T-G
• rs450320
• NM_005245.4:c.3581-4219A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005245.4(FAT1):​c.3581-4219A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,024 control chromosomes in the GnomAD database, including 2,908 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 0.18 (2908 hom., cov: 31)
• Consequence: FAT1 NM_005245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.589
• Publications: 6 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 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.3581-4219A>C		intron	N/A	NP_005236.2
	FAT1	NM_001440456.1		c.3581-4219A>C		intron	N/A	NP_001427385.1
	FAT1	NM_001440457.1		c.3581-4219A>C		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.3581-4219A>C		intron	N/A	ENSP00000406229.2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26781 AN: 151906 Hom.: 2903 Cov.: 31

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.154

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.176 AC: 26812 AN: 152024 Hom.: 2908 Cov.: 31 AF XY: 0.183 AC XY: 13594 AN XY: 74302

African (AFR) AF: 0.248 AC: 10257 AN: 41430

American (AMR) AF: 0.269 AC: 4113 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 383 AN: 3470

East Asian (EAS) AF: 0.428 AC: 2208 AN: 5158

South Asian (SAS) AF: 0.103 AC: 496 AN: 4828

European-Finnish (FIN) AF: 0.170 AC: 1792 AN: 10558

Middle Eastern (MID) AF: 0.155 AC: 45 AN: 290

European-Non Finnish (NFE) AF: 0.105 AC: 7129 AN: 67992

Other (OTH) AF: 0.166 AC: 350 AN: 2112

Alfa AF: 0.133 Hom.: 3800

Bravo AF: 0.195

Asia WGS AF: 0.271 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.3
DANN	Benign	0.78
PhyloP100		0.59
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: rs450320; hg19: chr4-187565156;