rs2306987

Variant names:

• chr4-186595501-T-A
• rs2306987
• NM_005245.4:c.13138+188A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-186595501-T-A
• chr4-186595501-T-C
• chr4-186595501-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005245.4(FAT1):​c.13138+188A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,068 control chromosomes in the GnomAD database, including 7,167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.30 (7167 hom., cov: 32)
• Consequence: FAT1 NM_005245.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.620
• 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]

FAT1 Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis

  Inheritance: AR Classification: STRONG Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 4-186595501-T-A is Benign according to our data. Variant chr4-186595501-T-A is described in ClinVar as Benign. ClinVar VariationId is 1272616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 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.13138+188A>T		intron	N/A	NP_005236.2	Q14517
	FAT1	NM_001440456.1		c.13138+188A>T		intron	N/A	NP_001427385.1
	FAT1	NM_001440457.1		c.13138+188A>T		intron	N/A	NP_001427386.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAT1	ENST00000441802.7	TSL:5 MANE Select	c.13138+188A>T		intron	N/A	ENSP00000406229.2	Q14517
	FAT1	ENST00000509927.1	TSL:1	c.112+188A>T		intron	N/A	ENSP00000420869.1	H0Y8F5
	FAT1	ENST00000917425.1		c.13138+188A>T		intron	N/A	ENSP00000587484.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45605 AN: 151950 Hom.: 7163 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.300 AC: 45612 AN: 152068 Hom.: 7167 Cov.: 32 AF XY: 0.300 AC XY: 22338 AN XY: 74336

African (AFR) AF: 0.234 AC: 9690 AN: 41490

American (AMR) AF: 0.377 AC: 5763 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1472 AN: 3468

East Asian (EAS) AF: 0.395 AC: 2038 AN: 5164

South Asian (SAS) AF: 0.234 AC: 1123 AN: 4806

European-Finnish (FIN) AF: 0.286 AC: 3020 AN: 10576

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21467 AN: 67964

Other (OTH) AF: 0.324 AC: 684 AN: 2112

Alfa AF: 0.135 Hom.: 248

Bravo AF: 0.306

Asia WGS AF: 0.283 AC: 987 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.19
DANN	Benign	0.52
PhyloP100		-0.62
PromoterAI		-0.014	Neutral
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2306987;

hg19: chr4-187516655;

COSMIC: COSV107530473;

COSMIC: COSV107530473;