rs2286948

Positions:

• chr19-49813497-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011527341.3(FUZ):​c.-191G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 345,758 control chromosomes in the GnomAD database, including 20,428 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 0.29 (7779 hom., cov: 33)
  • Exomes 𝑓: 0.35 (12649 hom.)
• Consequence: FUZ XM_011527341.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700

Genes affected

FUZ (HGNC:26219): (fuzzy planar cell polarity protein) This gene encodes a planar cell polarity protein that is involved in ciliogenesis and directional cell movement. Knockout studies in mice exhibit neural tube defects and defective cilia, and mutations in this gene are associated with neural tube defects in humans. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FUZ	XM_011527341.3	c.-191G>A		5_prime_UTR_variant	1/11		XP_011525643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FUZ	ENST00000529302.1	c.-167+110G>A		intron_variant		5		ENSP00000471793

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44394 AN: 152072 Hom.: 7769 Cov.: 33

Gnomad AFR AF: 0.0884

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.310

GnomAD4 exome AF: 0.351 AC: 67945 AN: 193568 Hom.: 12649 Cov.: 0 AF XY: 0.349 AC XY: 36426 AN XY: 104466

Gnomad4 AFR exome AF: 0.0832

Gnomad4 AMR exome AF: 0.453

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.519

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.347

GnomAD4 genome AF: 0.292 AC: 44404 AN: 152190 Hom.: 7779 Cov.: 33 AF XY: 0.296 AC XY: 22018 AN XY: 74396

Gnomad4 AFR AF: 0.0881

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.308

Alfa AF: 0.350 Hom.: 13046

Bravo AF: 0.287

Asia WGS AF: 0.394 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.2
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2286948; hg19: chr19-50316754;