rs2286948

Variant names:

• chr19-49813497-C-T
• rs2286948
• XM_011527341.3:c.-191G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

FUZ Gene-Disease associations (from GenCC):

• neural tube defects, susceptibility to

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FUZ	NM_025129.5	c.-391G>A		upstream_gene_variant		ENST00000313777.9	NP_079405.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUZ	ENST00000313777.9	c.-391G>A		upstream_gene_variant		1	NM_025129.5	ENSP00000313309.4

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

African (AFR) AF: 0.0832 AC: 465 AN: 5590

American (AMR) AF: 0.453 AC: 4204 AN: 9288

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 1281 AN: 4934

East Asian (EAS) AF: 0.519 AC: 4212 AN: 8122

South Asian (SAS) AF: 0.327 AC: 11811 AN: 36166

European-Finnish (FIN) AF: 0.401 AC: 3546 AN: 8840

Middle Eastern (MID) AF: 0.354 AC: 247 AN: 698

European-Non Finnish (NFE) AF: 0.352 AC: 38813 AN: 110236

Other (OTH) AF: 0.347 AC: 3366 AN: 9694

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

African (AFR) AF: 0.0881 AC: 3659 AN: 41514

American (AMR) AF: 0.392 AC: 5995 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 961 AN: 3468

East Asian (EAS) AF: 0.511 AC: 2650 AN: 5188

South Asian (SAS) AF: 0.332 AC: 1601 AN: 4828

European-Finnish (FIN) AF: 0.401 AC: 4239 AN: 10576

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.357 AC: 24250 AN: 68008

Other (OTH) AF: 0.308 AC: 651 AN: 2114

Alfa AF: 0.344 Hom.: 15837

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
PhyloP100		-0.0070
PromoterAI		-0.12	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2286948; hg19: chr19-50316754;