rs2306987

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAT1	NM_005245.4	c.13138+188A>T		intron_variant		ENST00000441802.7	NP_005236.2
FAT1	XM_005262834.4	c.13138+188A>T		intron_variant			XP_005262891.1
FAT1	XM_005262835.3	c.13138+188A>T		intron_variant			XP_005262892.1
FAT1	XM_006714139.4	c.13138+188A>T		intron_variant			XP_006714202.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAT1	ENST00000441802.7	c.13138+188A>T		intron_variant		5	NM_005245.4	ENSP00000406229	P1

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

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.324

Alfa AF: 0.135 Hom.: 248

Bravo AF: 0.306

Asia WGS AF: 0.283 AC: 987 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.19
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs2306987; hg19: chr4-187516655;