Variant 7-2525649-C-T 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.736-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 1,611,928 control chromosomes in the GnomAD database, including 4,276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 528 hom., cov: 33)

Exomes 𝑓: 0.068 ( 3748 hom. )

Consequence

LFNG
NM_001040167.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.388

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:

LFNG (HGNC:):

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=-0.83).

BP6

Variant 7-2525649-C-T is Benign according to our data. Variant chr7-2525649-C-T is described in ClinVar as [Benign]. Clinvar id is 257269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
LFNG	NM_001040167.2 linkuse as main transcript	c.736-36C>T	intron_variant	ENST00000222725.10	NP_001035257.1	Q8NES3-1
LFNG	NM_001040168.2 linkuse as main transcript	c.736-36C>T	intron_variant		NP_001035258.1	Q8NES3-3
LFNG	NM_001166355.2 linkuse as main transcript	c.523-36C>T	intron_variant		NP_001159827.1	Q8NES3-4
LFNG	NM_002304.3 linkuse as main transcript	c.349-36C>T	intron_variant		NP_002295.1	Q8NES3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000222725.10 linkuse as main transcript	c.736-36C>T		intron_variant		5	NM_001040167.2	ENSP00000222725.5		Q8NES3-1

Frequencies

GnomAD3 genomes

AF:

0.0789

AC:

12006

AN:

152232

Hom.:

527

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0889

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.0744

Gnomad ASJ

AF:

0.0380

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.0805

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0651

Gnomad OTH

AF:

0.0788

GnomAD3 exomes

AF:

0.0802

AC:

19873

AN:

247860

Hom.:

878

AF XY:

0.0790

AC XY:

10642

AN XY:

134706

show subpopulations

Gnomad AFR exome

AF:

0.0890

Gnomad AMR exome

AF:

0.0880

Gnomad ASJ exome

AF:

0.0431

Gnomad EAS exome

AF:

0.113

Gnomad SAS exome

AF:

0.0793

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.0651

Gnomad OTH exome

AF:

0.0763

GnomAD4 exome

AF:

0.0683

AC:

99727

AN:

1459580

Hom.:

3748

Cov.:

AF XY:

0.0685

AC XY:

49720

AN XY:

726138

show subpopulations

Gnomad4 AFR exome

AF:

0.0841

Gnomad4 AMR exome

AF:

0.0863

Gnomad4 ASJ exome

AF:

0.0430

Gnomad4 EAS exome

AF:

0.108

Gnomad4 SAS exome

AF:

0.0776

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.0627

Gnomad4 OTH exome

AF:

0.0687

GnomAD4 genome

AF:

0.0788

AC:

12011

AN:

152348

Hom.:

528

Cov.:

AF XY:

0.0817

AC XY:

6083

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0888

Gnomad4 AMR

AF:

0.0743

Gnomad4 ASJ

AF:

0.0380

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.0802

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.0651

Gnomad4 OTH

AF:

0.0789

Alfa

AF:

0.0695

Hom.:

Bravo

AF:

0.0768

Asia WGS

AF:

0.0980

AC:

342

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

Jan 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.7

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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