Variant rs13225716 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001040167.2(LFNG):c.988-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 1,598,972 control chromosomes in the GnomAD database, including 5,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 428 hom., cov: 32)

Exomes 𝑓: 0.083 ( 5518 hom. )

Consequence

LFNG
NM_001040167.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.195

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 7-2526799-G-A is Benign according to our data. Variant chr7-2526799-G-A is described in ClinVar as [Benign]. Clinvar id is 257272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
LFNG	NM_001040167.2 linkuse as main transcript	c.988-37G>A	intron_variant	ENST00000222725.10	NP_001035257.1
LFNG	NM_001040168.2 linkuse as main transcript	c.988-37G>A	intron_variant		NP_001035258.1
LFNG	NM_001166355.2 linkuse as main transcript	c.775-37G>A	intron_variant		NP_001159827.1
LFNG	NM_002304.3 linkuse as main transcript	c.601-37G>A	intron_variant		NP_002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000222725.10 linkuse as main transcript	c.988-37G>A		intron_variant		5	NM_001040167.2	ENSP00000222725	P1	Q8NES3-1

Frequencies

GnomAD3 genomes

AF:

0.0626

AC:

9516

AN:

152042

Hom.:

426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0180

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0620

Gnomad EAS

AF:

0.00213

Gnomad SAS

AF:

0.0265

Gnomad FIN

AF:

0.0535

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0878

Gnomad OTH

AF:

0.0645

GnomAD3 exomes

AF:

0.0702

AC:

16906

AN:

240754

Hom.:

787

AF XY:

0.0680

AC XY:

8976

AN XY:

132062

show subpopulations

Gnomad AFR exome

AF:

0.0144

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.0576

Gnomad EAS exome

AF:

0.00134

Gnomad SAS exome

AF:

0.0280

Gnomad FIN exome

AF:

0.0596

Gnomad NFE exome

AF:

0.0852

Gnomad OTH exome

AF:

0.0719

GnomAD4 exome

AF:

0.0826

AC:

119501

AN:

1446810

Hom.:

5518

Cov.:

AF XY:

0.0809

AC XY:

58293

AN XY:

720466

show subpopulations

Gnomad4 AFR exome

AF:

0.0136

Gnomad4 AMR exome

AF:

0.128

Gnomad4 ASJ exome

AF:

0.0560

Gnomad4 EAS exome

AF:

0.000936

Gnomad4 SAS exome

AF:

0.0303

Gnomad4 FIN exome

AF:

0.0594

Gnomad4 NFE exome

AF:

0.0925

Gnomad4 OTH exome

AF:

0.0706

GnomAD4 genome

AF:

0.0626

AC:

9529

AN:

152162

Hom.:

428

Cov.:

AF XY:

0.0605

AC XY:

4499

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0180

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.0620

Gnomad4 EAS

AF:

0.00194

Gnomad4 SAS

AF:

0.0263

Gnomad4 FIN

AF:

0.0535

Gnomad4 NFE

AF:

0.0878

Gnomad4 OTH

AF:

0.0648

Alfa

AF:

0.0754

Hom.:

104

Bravo

AF:

0.0647

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.9

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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