rs2276930

Variant names:

• chr4-186724024-G-A
• rs2276930
• ENST00000509647.1:c.-19+2330C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000509647.1(FAT1):​c.-19+2330C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000521 in 151,688 control chromosomes in the GnomAD database, including 2 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 0.00052 (2 hom., cov: 28)
• Consequence: FAT1 ENST00000509647.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 2 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]

ENSG00000294511 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000521 (79/151688) while in subpopulation EAS AF = 0.0116 (59/5102). AF 95% confidence interval is 0.0092. There are 2 homozygotes in GnomAd4. There are 46 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT1	NM_001440456.1	c.-19+2330C>T		intron_variant	Intron 1 of 27		NP_001427385.1
FAT1	NM_001440455.1	c.-19+2330C>T		intron_variant	Intron 1 of 26		NP_001427384.1
FAT1	NM_005245.4	c.-379C>T		upstream_gene_variant		ENST00000441802.7	NP_005236.2
FAT1	NM_001440457.1	c.-379C>T		upstream_gene_variant			NP_001427386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT1	ENST00000509647.1	c.-19+2330C>T		intron_variant	Intron 1 of 1	1		ENSP00000423736.1
ENSG00000294511	ENST00000724016.1	n.88G>A		non_coding_transcript_exon_variant	Exon 1 of 3
FAT1	ENST00000441802.7	c.-379C>T		upstream_gene_variant		5	NM_005245.4	ENSP00000406229.2

Frequencies

GnomAD3 genomes AF: 0.000521 AC: 79 AN: 151582 Hom.: 2 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.000479

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

GnomAD4 genome AF: 0.000521 AC: 79 AN: 151688 Hom.: 2 Cov.: 28 AF XY: 0.000620 AC XY: 46 AN XY: 74152

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.0000655 AC: 1 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.0116 AC: 59 AN: 5102

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10462

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000133 AC: 9 AN: 67884

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000299 Hom.: 0

Bravo AF: 0.000340

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.71
DANN	Benign	0.82
PhyloP100		-1.1
PromoterAI		0.076	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2276930; hg19: chr4-187645178;