Variant 7-2513352-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0140

Variant links:

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]

LFNG links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
LFNG	NM_001166355.2 linkuse as main transcript	c.219+24A>C		intron_variant			NP_001159827.1	Q8NES3-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000402506.5 linkuse as main transcript	c.219+24A>C		intron_variant		2		ENSP00000385764.1		Q8NES3-4

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44214

AN:

152020

Hom.:

7071

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.349

AC XY:

242985

AN XY:

696024

show subpopulations

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.:

AF XY:

0.294

AC XY:

21841

AN XY:

74366

show subpopulations

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

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over