Variant 7-2519788-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001040167.2(LFNG):c.-74C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 900,606 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0098 ( 21 hom., cov: 32)

Exomes 𝑓: 0.00072 ( 11 hom. )

Consequence

LFNG
NM_001040167.2 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.40

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=-0.78).

BP6

Variant 7-2519788-C-G is Benign according to our data. Variant chr7-2519788-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1706904.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00981 (1463/149090) while in subpopulation AFR AF= 0.0339 (1396/41240). AF 95% confidence interval is 0.0324. There are 21 homozygotes in gnomad4. There are 706 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
LFNG	NM_001040167.2 linkuse as main transcript	c.-74C>G	5_prime_UTR_variant	1/8	ENST00000222725.10	NP_001035257.1
LFNG	NM_001040168.2 linkuse as main transcript	c.-74C>G	5_prime_UTR_variant	1/8		NP_001035258.1
LFNG	NM_001166355.2 linkuse as main transcript	c.220-4907C>G	intron_variant			NP_001159827.1
LFNG	NM_002304.3 linkuse as main transcript	c.45+1190C>G	intron_variant			NP_002295.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000222725.10 linkuse as main transcript	c.-74C>G	5_prime_UTR_variant	1/8	5	NM_001040167.2	ENSP00000222725	P1	Q8NES3-1
LFNG	ENST00000338732.7 linkuse as main transcript	c.45+1190C>G	intron_variant		1		ENSP00000343095		Q8NES3-2
LFNG	ENST00000402045.5 linkuse as main transcript	c.45+1190C>G	intron_variant		1		ENSP00000384786		Q8NES3-2
LFNG	ENST00000402506.5 linkuse as main transcript	c.220-4907C>G	intron_variant		2		ENSP00000385764		Q8NES3-4

Frequencies

GnomAD3 genomes

AF:

0.00981

AC:

1462

AN:

148984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00346

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000449

Gnomad OTH

AF:

0.00585

GnomAD4 exome

AF:

0.000723

AC:

543

AN:

751516

Hom.:

AF XY:

0.000635

AC XY:

223

AN XY:

351248

show subpopulations

Gnomad4 AFR exome

AF:

0.0341

Gnomad4 AMR exome

AF:

0.00549

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000353

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00981

AC:

1463

AN:

149090

Hom.:

Cov.:

AF XY:

0.00971

AC XY:

706

AN XY:

72736

show subpopulations

Gnomad4 AFR

AF:

0.0339

Gnomad4 AMR

AF:

0.00345

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000449

Gnomad4 OTH

AF:

0.00579

Alfa

AF:

0.00202

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 25, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.20

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