7-2526206-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001040167.2(LFNG):c.822-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,609,138 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 47 hom. )

Consequence

LFNG
NM_001040167.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.78

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-2526206-C-T is Benign according to our data. Variant chr7-2526206-C-T is described in ClinVar as [Benign]. Clinvar id is 257270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00203 (309/152326) while in subpopulation EAS AF= 0.0487 (252/5178). AF 95% confidence interval is 0.0437. There are 8 homozygotes in gnomad4. There are 161 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
LFNG	NM_001040167.2 linkuse as main transcript	c.822-38C>T	intron_variant	ENST00000222725.10
LFNG	NM_001040168.2 linkuse as main transcript	c.822-38C>T	intron_variant
LFNG	NM_001166355.2 linkuse as main transcript	c.609-38C>T	intron_variant
LFNG	NM_002304.3 linkuse as main transcript	c.435-38C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LFNG	ENST00000222725.10 linkuse as main transcript	c.822-38C>T		intron_variant		5	NM_001040167.2	P1	Q8NES3-1

Frequencies

GnomAD3 genomes

AF:

0.00205

AC:

312

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0491

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00462

AC:

1140

AN:

246806

Hom.:

AF XY:

0.00418

AC XY:

562

AN XY:

134298

show subpopulations

Gnomad AFR exome

AF:

0.000315

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0574

Gnomad SAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.0000493

Gnomad NFE exome

AF:

0.000216

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00151

AC:

2194

AN:

1456812

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

1033

AN XY:

724946

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0427

Gnomad4 SAS exome

AF:

0.00182

Gnomad4 FIN exome

AF:

0.0000397

Gnomad4 NFE exome

AF:

0.0000856

Gnomad4 OTH exome

AF:

0.00383

GnomAD4 genome

AF:

0.00203

AC:

309

AN:

152326

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

161

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0487

Gnomad4 SAS

AF:

0.00476

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000323

Hom.:

Bravo

AF:

0.00254

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

May 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

Cadd

Benign

2.6

Dann

Benign

0.87

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