7-2513352-A-C

Variant summary

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

The NM_001166355.2(LFNG):c.219+24A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,564,848 control chromosomes in the GnomAD database, including 93,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7088 hom., cov: 33)
  • Exomes 𝑓: 0.34 (86448 hom.)
• Consequence: LFNG NM_001166355.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0140

Genes affected

LFNG (HGNC:6560): (LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase) This gene is a member of the glycosyltransferase 31 gene family. Members of this gene family, which also includes the MFNG (GeneID: 4242) and RFNG (GeneID: 5986) genes, encode evolutionarily conserved glycosyltransferases that act in the Notch signaling pathway to define boundaries during embryonic development. While their genomic structure is distinct from other glycosyltransferases, these proteins have a fucose-specific beta-1,3-N-acetylglucosaminyltransferase activity that leads to elongation of O-linked fucose residues on Notch, which alters Notch signaling. The protein encoded by this gene is predicted to be a single-pass type II Golgi membrane protein but it may also be secreted and proteolytically processed like the related proteins in mouse and Drosophila (PMID: 9187150). Mutations in this gene have been associated with autosomal recessive spondylocostal dysostosis 3. [provided by RefSeq, May 2018]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-2513352-A-C is Benign according to our data. Variant chr7-2513352-A-C is described in ClinVar as [Benign]. Clinvar id is 1224973.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LFNG	NM_001166355.2	c.219+24A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LFNG	ENST00000402506.5	c.219+24A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44214 AN: 152020 Hom.: 7071 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.304

GnomAD3 exomes AF: 0.319 AC: 67395 AN: 211020 Hom.: 11382 AF XY: 0.331 AC XY: 37404 AN XY: 112944

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.259

Gnomad ASJ exome AF: 0.337

Gnomad EAS exome AF: 0.134

Gnomad SAS exome AF: 0.457

Gnomad FIN exome AF: 0.365

Gnomad NFE exome AF: 0.353

Gnomad OTH exome AF: 0.342

GnomAD4 exome AF: 0.345 AC: 486969 AN: 1412708 Hom.: 86448 Cov.: 34 AF XY: 0.349 AC XY: 242985 AN XY: 696024

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.260

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.451

Gnomad4 FIN exome AF: 0.363

Gnomad4 NFE exome AF: 0.353

Gnomad4 OTH exome AF: 0.344

GnomAD4 genome AF: 0.291 AC: 44272 AN: 152140 Hom.: 7088 Cov.: 33 AF XY: 0.294 AC XY: 21841 AN XY: 74366

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.311

Alfa AF: 0.324 Hom.: 8472

Bravo AF: 0.275

Asia WGS AF: 0.339 AC: 1178 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

Jul 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.9
Dann	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs286560; hg19: chr7-2552986; COSMIC: COSV67864594; COSMIC: COSV67864594;