Variant 7-2512747-G-A 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.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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.122

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 7-2512747-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	Protein	UniProt
LFNG	NM_001166355.2 linkuse as main transcript	c.47+46G>A		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.47+46G>A		intron_variant		2		ENSP00000385764.1		Q8NES3-4

Frequencies

GnomAD3 genomes

AF:

0.0143

AC:

2171

AN:

152062

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.00809

AC XY:

5775

AN XY:

714208

show subpopulations

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.:

Cov.:

AF XY:

0.0165

AC XY:

1228

AN XY:

74412

show subpopulations

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.:

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

LINK: link

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

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