7-2519788-C-G

Variant names:

• chr7-2519788-C-G
• rs532218283
• NM_001040167.2:c.-74C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.40

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LFNG	NM_001040167.2	c.-74C>G		5_prime_UTR_variant	Exon 1 of 8	ENST00000222725.10	NP_001035257.1
LFNG	NM_001040168.2	c.-74C>G		5_prime_UTR_variant	Exon 1 of 8		NP_001035258.1
LFNG	NM_001166355.2	c.220-4907C>G		intron_variant	Intron 2 of 8		NP_001159827.1
LFNG	NM_002304.3	c.45+1190C>G		intron_variant	Intron 2 of 8		NP_002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000222725	c.-74C>G		5_prime_UTR_variant	Exon 1 of 8	5	NM_001040167.2	ENSP00000222725.5

Frequencies

GnomAD3 genomes AF: 0.00981 AC: 1462 AN: 148984 Hom.: 21 Cov.: 32

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.: 11 AF XY: 0.000635 AC XY: 223 AN XY: 351248

Gnomad4 AFR exome AF: 0.0341 AC: 480 AN: 14092

Gnomad4 AMR exome AF: 0.00549 AC: 8 AN: 1456

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 5286

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 6038

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 14976

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 3122

Gnomad4 NFE exome AF: 0.0000353 AC: 24 AN: 679680

Gnomad4 Remaining exome AF: 0.00123 AC: 31 AN: 25266

GnomAD4 genome AF: 0.00981 AC: 1463 AN: 149090 Hom.: 21 Cov.: 32 AF XY: 0.00971 AC XY: 706 AN XY: 72736

Gnomad4 AFR AF: 0.0339 AC: 0.0338506 AN: 0.0338506

Gnomad4 AMR AF: 0.00345 AC: 0.0034524 AN: 0.0034524

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000449 AC: 0.0000449438 AN: 0.0000449438

Gnomad4 OTH AF: 0.00579 AC: 0.00579151 AN: 0.00579151

Alfa AF: 0.00202 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 25, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.20
Mutation Taster		=100/0	polymorphism

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs532218283; hg19: chr7-2559422;