7-2512747-G-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+46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00785 in 1,584,676 control chromosomes in the GnomAD database, including 364 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (46 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (318 hom.)
• Consequence: LFNG NM_001166355.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.122

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 7-2512747-G-A is Benign according to our data. Variant chr7-2512747-G-A is described in ClinVar as [Benign]. Clinvar id is 1222276.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LFNG	NM_001166355.2	c.47+46G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LFNG	ENST00000402506.5	c.47+46G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2171 AN: 152062 Hom.: 45 Cov.: 32

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0391

Gnomad SAS AF: 0.0636

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000427

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.0198 AC: 4826 AN: 243656 Hom.: 155 AF XY: 0.0190 AC XY: 2525 AN XY: 132810

Gnomad AFR exome AF: 0.0261

Gnomad AMR exome AF: 0.0566

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0411

Gnomad SAS exome AF: 0.0550

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000412

Gnomad OTH exome AF: 0.0110

GnomAD4 exome AF: 0.00716 AC: 10252 AN: 1432496 Hom.: 318 Cov.: 25 AF XY: 0.00809 AC XY: 5775 AN XY: 714208

Gnomad4 AFR exome AF: 0.0228

Gnomad4 AMR exome AF: 0.0541

Gnomad4 ASJ exome AF: 0.0000386

Gnomad4 EAS exome AF: 0.0470

Gnomad4 SAS exome AF: 0.0510

Gnomad4 FIN exome AF: 0.000113

Gnomad4 NFE exome AF: 0.000280

Gnomad4 OTH exome AF: 0.00921

GnomAD4 genome AF: 0.0143 AC: 2182 AN: 152180 Hom.: 46 Cov.: 32 AF XY: 0.0165 AC XY: 1228 AN XY: 74412

Gnomad4 AFR AF: 0.0249

Gnomad4 AMR AF: 0.0379

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0394

Gnomad4 SAS AF: 0.0636

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000427

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00388 Hom.: 3

Bravo AF: 0.0161

Asia WGS AF: 0.0620 AC: 216 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.3
Dann	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs115380608; hg19: chr7-2552381;