rs4122086

Variant names:

• chr11-92697680-G-A
• rs4122086
• NM_001367949.2:c.3669+235G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367949.2(FAT3):​c.3669+235G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 152,276 control chromosomes in the GnomAD database, including 239 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 0.037 (239 hom., cov: 32)
• Consequence: FAT3 NM_001367949.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820
• Publications: 1 publications found

Genes affected

FAT3 (HGNC:23112): (FAT atypical cadherin 3) Predicted to enable calcium ion binding activity. Predicted to be involved in cell-cell adhesion. Predicted to act upstream of or within several processes, including negative regulation of dendrite development; neuron migration; and retina layer formation. Predicted to be located in dendrite and plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAT3	NM_001367949.2	c.3669+235G>A		intron_variant	Intron 4 of 27	ENST00000525166.6	NP_001354878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAT3	ENST00000525166.6	c.3669+235G>A		intron_variant	Intron 4 of 27	5	NM_001367949.2	ENSP00000432586.2
FAT3	ENST00000409404.6	c.3669+235G>A		intron_variant	Intron 3 of 24	5		ENSP00000387040.2

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5559 AN: 152158 Hom.: 239 Cov.: 32

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0177

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.0971

Gnomad FIN AF: 0.0473

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.00916

Gnomad OTH AF: 0.0382

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

GnomAD4 genome AF: 0.0365 AC: 5563 AN: 152276 Hom.: 239 Cov.: 32 AF XY: 0.0398 AC XY: 2962 AN XY: 74456

African (AFR) AF: 0.0545 AC: 2264 AN: 41550

American (AMR) AF: 0.0176 AC: 270 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 268 AN: 3470

East Asian (EAS) AF: 0.207 AC: 1071 AN: 5166

South Asian (SAS) AF: 0.0968 AC: 467 AN: 4826

European-Finnish (FIN) AF: 0.0473 AC: 502 AN: 10610

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.00917 AC: 624 AN: 68026

Other (OTH) AF: 0.0369 AC: 78 AN: 2114

Alfa AF: 0.0208 Hom.: 20

Bravo AF: 0.0339

Asia WGS AF: 0.115 AC: 398 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.1
DANN	Benign	0.44
PhyloP100		-0.082
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4122086; hg19: chr11-92430846;