7-2513589-A-G

Position:

• chr7-2513589-A-G

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+261A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0839 in 151,950 control chromosomes in the GnomAD database, including 1,241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.084 (1241 hom., cov: 33)
• Consequence: LFNG NM_001166355.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.221

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=-0.8).
• BP6: Variant 7-2513589-A-G is Benign according to our data. Variant chr7-2513589-A-G is described in ClinVar as [Benign]. Clinvar id is 1279690.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LFNG	NM_001166355.2	c.219+261A>G		intron_variant			NP_001159827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000402506.5	c.219+261A>G		intron_variant		2		ENSP00000385764

Frequencies

GnomAD3 genomes AF: 0.0839 AC: 12737 AN: 151832 Hom.: 1243 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0713

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.00293

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00667

Gnomad OTH AF: 0.0735

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

GnomAD4 genome AF: 0.0839 AC: 12749 AN: 151950 Hom.: 1241 Cov.: 33 AF XY: 0.0852 AC XY: 6331 AN XY: 74286

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.0715

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.00293

Gnomad4 NFE AF: 0.00666

Gnomad4 OTH AF: 0.0727

Alfa AF: 0.0480 Hom.: 78

Bravo AF: 0.0948

Asia WGS AF: 0.139 AC: 485 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	-0.80
CADD	Benign	0.92
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs60335938; hg19: chr7-2553223;