4-186588576-T-TG

Variant names:

• chr4-186588576-T-TG
• rs147542447
• NM_005245.4:c.*15dupC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005245.4(FAT1):​c.*15dupC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,599,144 control chromosomes in the GnomAD database, including 228 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (114 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (114 hom.)
• Consequence: FAT1 NM_005245.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.17
• Publications: 0 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]

FAT1 Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis

  Inheritance: AR Classification: STRONG Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 4-186588576-T-TG is Benign according to our data. Variant chr4-186588576-T-TG is described in ClinVar as Benign. ClinVar VariationId is 1262812.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0689 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAT1	NM_005245.4	MANE Select	c.*15dupC		3_prime_UTR	Exon 27 of 27	NP_005236.2	Q14517
	FAT1	NM_001440456.1		c.*15dupC		3_prime_UTR	Exon 28 of 28	NP_001427385.1
	FAT1	NM_001440457.1		c.*15dupC		3_prime_UTR	Exon 28 of 28	NP_001427386.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAT1	ENST00000441802.7	TSL:5 MANE Select	c.*15dupC		3_prime_UTR	Exon 27 of 27	ENSP00000406229.2	Q14517
	FAT1	ENST00000917425.1		c.*15dupC		3_prime_UTR	Exon 27 of 27	ENSP00000587484.1
	FAT1	ENST00000917424.1		c.*15dupC		3_prime_UTR	Exon 27 of 27	ENSP00000587483.1

Frequencies

GnomAD3 genomes AF: 0.0214 AC: 3256 AN: 152044 Hom.: 112 Cov.: 32

Gnomad AFR AF: 0.0709

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00701

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00724 AC: 1719 AN: 237402 AF XY: 0.00569

Gnomad AFR exome AF: 0.0738

Gnomad AMR exome AF: 0.00307

Gnomad ASJ exome AF: 0.0447

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000566

Gnomad OTH exome AF: 0.00452

GnomAD4 exome AF: 0.00324 AC: 4686 AN: 1446982 Hom.: 114 Cov.: 31 AF XY: 0.00290 AC XY: 2084 AN XY: 718240

African (AFR) AF: 0.0750 AC: 2498 AN: 33312

American (AMR) AF: 0.00356 AC: 157 AN: 44102

Ashkenazi Jewish (ASJ) AF: 0.0451 AC: 1121 AN: 24834

East Asian (EAS) AF: 0.00 AC: 0 AN: 39590

South Asian (SAS) AF: 0.000251 AC: 21 AN: 83586

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52320

Middle Eastern (MID) AF: 0.00461 AC: 22 AN: 4772

European-Non Finnish (NFE) AF: 0.000345 AC: 381 AN: 1104758

Other (OTH) AF: 0.00812 AC: 485 AN: 59708

GnomAD4 genome AF: 0.0215 AC: 3273 AN: 152162 Hom.: 114 Cov.: 32 AF XY: 0.0207 AC XY: 1541 AN XY: 74398

African (AFR) AF: 0.0711 AC: 2949 AN: 41502

American (AMR) AF: 0.00700 AC: 107 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 147 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68010

Other (OTH) AF: 0.0137 AC: 29 AN: 2112

Alfa AF: 0.0176 Hom.: 11

Bravo AF: 0.0251

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
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: rs147542447; hg19: chr4-187509730;