7-2512784-C-A

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.47+83C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00963 in 1,186,160 control chromosomes in the GnomAD database, including 301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (63 hom., cov: 32)
  • Exomes 𝑓: 0.0084 (238 hom.)
• Consequence: LFNG NM_001166355.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.651

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=-0.87).
• BP6: Variant 7-2512784-C-A is Benign according to our data. Variant chr7-2512784-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1325938.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LFNG	NM_001166355.2	c.47+83C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LFNG	ENST00000402506.5	c.47+83C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2705 AN: 152036 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.0383

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0395

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0398

Gnomad SAS AF: 0.0509

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0144

GnomAD4 exome AF: 0.00843 AC: 8713 AN: 1034006 Hom.: 238 AF XY: 0.00913 AC XY: 4839 AN XY: 530006

Gnomad4 AFR exome AF: 0.0374

Gnomad4 AMR exome AF: 0.0545

Gnomad4 ASJ exome AF: 0.0000433

Gnomad4 EAS exome AF: 0.0475

Gnomad4 SAS exome AF: 0.0414

Gnomad4 FIN exome AF: 0.000116

Gnomad4 NFE exome AF: 0.000353

Gnomad4 OTH exome AF: 0.00998

GnomAD4 genome AF: 0.0178 AC: 2715 AN: 152154 Hom.: 63 Cov.: 32 AF XY: 0.0194 AC XY: 1441 AN XY: 74398

Gnomad4 AFR AF: 0.0383

Gnomad4 AMR AF: 0.0396

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0400

Gnomad4 SAS AF: 0.0507

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00160 Hom.: 0

Bravo AF: 0.0208

Asia WGS AF: 0.0570 AC: 196 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.3
Dann	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs115158697; hg19: chr7-2552418;