7-2513396-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001166355.2(LFNG):c.219+68T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 1,478,784 control chromosomes in the GnomAD database, including 2,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.045 (246 hom., cov: 34)
  • Exomes 𝑓: 0.054 (2258 hom.)
• Consequence: LFNG NM_001166355.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.17

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 7-2513396-T-C is Benign according to our data. Variant chr7-2513396-T-C is described in ClinVar as [Benign]. Clinvar id is 1272909.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LFNG	NM_001166355.2	c.219+68T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LFNG	ENST00000402506.5	c.219+68T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0454 AC: 6903 AN: 152178 Hom.: 245 Cov.: 34

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0960

Gnomad ASJ AF: 0.0456

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0128

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0493

GnomAD4 exome AF: 0.0543 AC: 71966 AN: 1326488 Hom.: 2258 AF XY: 0.0534 AC XY: 34728 AN XY: 650568

Gnomad4 AFR exome AF: 0.00781

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.0416

Gnomad4 EAS exome AF: 0.000348

Gnomad4 SAS exome AF: 0.0142

Gnomad4 FIN exome AF: 0.0639

Gnomad4 NFE exome AF: 0.0591

Gnomad4 OTH exome AF: 0.0450

GnomAD4 genome AF: 0.0454 AC: 6912 AN: 152296 Hom.: 246 Cov.: 34 AF XY: 0.0447 AC XY: 3328 AN XY: 74472

Gnomad4 AFR AF: 0.0105

Gnomad4 AMR AF: 0.0967

Gnomad4 ASJ AF: 0.0456

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.0597

Gnomad4 NFE AF: 0.0582

Gnomad4 OTH AF: 0.0488

Alfa AF: 0.0507 Hom.: 28

Bravo AF: 0.0466

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.13
Dann	Benign	0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs73049130; hg19: chr7-2553030;