rs61743870

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001040167.2(LFNG):c.1002C>T(p.Tyr334Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 1,612,152 control chromosomes in the GnomAD database, including 1,725 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 189 hom., cov: 32)

Exomes 𝑓: 0.029 ( 1536 hom. )

Consequence

LFNG
NM_001040167.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.59

Publications

6 publications found

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:

MIR4648 (HGNC:41560): (microRNA 4648) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR4648 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 7-2526850-C-T is Benign according to our data. Variant chr7-2526850-C-T is described in ClinVar as [Benign]. Clinvar id is 257264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LFNG	NM_001040167.2 link	c.1002C>T	p.Tyr334Tyr	synonymous_variant	Exon 7 of 8	ENST00000222725.10	NP_001035257.1	Q8NES3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000222725.10 link	c.1002C>T	p.Tyr334Tyr	synonymous_variant	Exon 7 of 8	5	NM_001040167.2	ENSP00000222725.5		Q8NES3-1

Frequencies

GnomAD3 genomes

AF:

0.0408

AC:

6186

AN:

151710

Hom.:

191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0513

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0459

Gnomad ASJ

AF:

0.0257

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.0574

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0180

Gnomad OTH

AF:

0.0484

GnomAD2 exomes

AF:

0.0516

AC:

12832

AN:

248882

AF XY:

0.0531

show subpopulations

Gnomad AFR exome

AF:

0.0516

Gnomad AMR exome

AF:

0.0507

Gnomad ASJ exome

AF:

0.0296

Gnomad EAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.0561

Gnomad NFE exome

AF:

0.0211

Gnomad OTH exome

AF:

0.0417

GnomAD4 exome

AF:

0.0295

AC:

43055

AN:

1460324

Hom.:

1536

Cov.:

AF XY:

0.0319

AC XY:

23165

AN XY:

726470

show subpopulations

African (AFR)

AF:

0.0524

AC:

1753

AN:

33470

American (AMR)

AF:

0.0511

AC:

2283

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0284

AC:

741

AN:

26116

East Asian (EAS)

AF:

0.150

AC:

5946

AN:

39698

South Asian (SAS)

AF:

0.112

AC:

9683

AN:

86242

European-Finnish (FIN)

AF:

0.0527

AC:

2746

AN:

52116

Middle Eastern (MID)

AF:

0.0699

AC:

403

AN:

5764

European-Non Finnish (NFE)

AF:

0.0154

AC:

17132

AN:

1111850

Other (OTH)

AF:

0.0392

AC:

2368

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

2408

4816

7225

9633

12041

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

788

1576

2364

3152

3940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0407

AC:

6186

AN:

151828

Hom.:

189

Cov.:

AF XY:

0.0441

AC XY:

3272

AN XY:

74146

show subpopulations

African (AFR)

AF:

0.0514

AC:

2129

AN:

41428

American (AMR)

AF:

0.0459

AC:

700

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0257

AC:

AN:

3464

East Asian (EAS)

AF:

0.141

AC:

721

AN:

5100

South Asian (SAS)

AF:

0.123

AC:

590

AN:

4810

European-Finnish (FIN)

AF:

0.0574

AC:

604

AN:

10520

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0180

AC:

1224

AN:

67938

Other (OTH)

AF:

0.0479

AC:

101

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

279

557

836

1114

1393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0262

Hom.:

189

Bravo

AF:

0.0387

Asia WGS

AF:

0.100

AC:

347

AN:

3478

EpiCase

AF:

0.0192

EpiControl

AF:

0.0226

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Spondylocostal dysostosis 3, autosomal recessive

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

-1.6

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over