Variant 7-2527893-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001040167.2(LFNG):c.*681C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 989,400 control chromosomes in the GnomAD database, including 4,389 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.065 ( 458 hom., cov: 31)

Exomes 𝑓: 0.095 ( 3931 hom. )

Consequence

LFNG
NM_001040167.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.748

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
LFNG	NM_001040167.2 linkuse as main transcript	c.*681C>G	3_prime_UTR_variant	8/8	ENST00000222725.10	NP_001035257.1	Q8NES3-1
LFNG	NM_001166355.2 linkuse as main transcript	c.*681C>G	3_prime_UTR_variant	9/9		NP_001159827.1	Q8NES3-4
LFNG	NM_002304.3 linkuse as main transcript	c.*681C>G	3_prime_UTR_variant	9/9		NP_002295.1	Q8NES3-2
LFNG	NM_001040168.2 linkuse as main transcript	c.1073+972C>G	intron_variant			NP_001035258.1	Q8NES3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000222725.10 linkuse as main transcript	c.*681C>G		3_prime_UTR_variant	8/8	5	NM_001040167.2	ENSP00000222725.5		Q8NES3-1

Frequencies

GnomAD3 genomes

AF:

0.0654

AC:

9944

AN:

152094

Hom.:

456

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0187

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.0645

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.0560

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0918

Gnomad OTH

AF:

0.0669

GnomAD4 exome

AF:

0.0945

AC:

79139

AN:

837188

Hom.:

3931

Cov.:

AF XY:

0.0944

AC XY:

36528

AN XY:

386864

show subpopulations

Gnomad4 AFR exome

AF:

0.0106

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.0516

Gnomad4 EAS exome

AF:

0.00240

Gnomad4 SAS exome

AF:

0.0296

Gnomad4 FIN exome

AF:

0.0789

Gnomad4 NFE exome

AF:

0.0992

Gnomad4 OTH exome

AF:

0.0758

GnomAD4 genome

AF:

0.0654

AC:

9958

AN:

152212

Hom.:

458

Cov.:

AF XY:

0.0630

AC XY:

4686

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0187

Gnomad4 AMR

AF:

0.115

Gnomad4 ASJ

AF:

0.0645

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0284

Gnomad4 FIN

AF:

0.0560

Gnomad4 NFE

AF:

0.0918

Gnomad4 OTH

AF:

0.0672

Alfa

AF:

0.0780

Hom.:

Bravo

AF:

0.0679

Asia WGS

AF:

0.0320

AC:

112

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.4

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over