7-2513549-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.219+221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0735 in 152,132 control chromosomes in the GnomAD database, including 961 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.074 (961 hom., cov: 34)
• Consequence: LFNG NM_001166355.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.889

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=-0.92).
• BP6: Variant 7-2513549-G-A is Benign according to our data. Variant chr7-2513549-G-A is described in ClinVar as [Benign]. Clinvar id is 1178773.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LFNG	NM_001166355.2	c.219+221G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LFNG	ENST00000402506.5	c.219+221G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0735 AC: 11174 AN: 152014 Hom.: 962 Cov.: 34

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0672

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.0868

Gnomad FIN AF: 0.00282

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00585

Gnomad OTH AF: 0.0641

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0735 AC: 11182 AN: 152132 Hom.: 961 Cov.: 34 AF XY: 0.0746 AC XY: 5552 AN XY: 74386

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.0674

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.0871

Gnomad4 FIN AF: 0.00282

Gnomad4 NFE AF: 0.00584

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0419 Hom.: 63

Bravo AF: 0.0835

Asia WGS AF: 0.130 AC: 454 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	-0.92
Cadd	Benign	0.081
Dann	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58469146; hg19: chr7-2553183;