4-125316086-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001291303.3(FAT4):c.-13+109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,016 control chromosomes in the GnomAD database, including 7,537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7537 hom., cov: 32)
• Consequence: FAT4 NM_001291303.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.891

Genes affected

FAT4 (HGNC:23109): (FAT atypical cadherin 4) The protein encoded by this gene is a member of the protocadherin family. This gene may play a role in regulating planar cell polarity (PCP). Studies in mice suggest that loss of PCP signaling may cause cystic kidney disease, and mutations in this gene have been associated with Van Maldergem Syndrome 2. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 4-125316086-A-G is Benign according to our data. Variant chr4-125316086-A-G is described in ClinVar as [Benign]. Clinvar id is 669952.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAT4	NM_001291303.3	c.-13+109A>G		intron_variant		ENST00000394329.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAT4	ENST00000394329.9	c.-13+109A>G		intron_variant		5	NM_001291303.3	P1
FAT4	ENST00000674496.2	c.-55+109A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46341 AN: 151898 Hom.: 7528 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.305 AC: 46376 AN: 152016 Hom.: 7537 Cov.: 32 AF XY: 0.303 AC XY: 22491 AN XY: 74298

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.306

Alfa AF: 0.342 Hom.: 2015

Bravo AF: 0.296

Asia WGS AF: 0.194 AC: 678 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	6.3
Dann	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7677005; hg19: chr4-126237241; COSMIC: COSV67900232;