rs13225716

Variant names:

• chr7-2526799-G-A
• rs13225716
• NM_001040167.2:c.988-37G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-2526799-G-A
• chr7-2526799-G-C
• chr7-2526799-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001040167.2(LFNG):​c.988-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 1,598,972 control chromosomes in the GnomAD database, including 5,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (428 hom., cov: 32)
  • Exomes 𝑓: 0.083 (5518 hom.)
• Consequence: LFNG NM_001040167.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.195
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• spondylocostal dysostosis 3, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive spondylocostal dysostosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-2526799-G-A is Benign according to our data. Variant chr7-2526799-G-A is described in ClinVar as Benign. ClinVar VariationId is 257272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LFNG	NM_001040167.2	c.988-37G>A		intron_variant	Intron 6 of 7	ENST00000222725.10	NP_001035257.1
LFNG	NM_001040168.2	c.988-37G>A		intron_variant	Intron 6 of 7		NP_001035258.1
LFNG	NM_001166355.2	c.775-37G>A		intron_variant	Intron 7 of 8		NP_001159827.1
LFNG	NM_002304.3	c.601-37G>A		intron_variant	Intron 7 of 8		NP_002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000222725.10	c.988-37G>A		intron_variant	Intron 6 of 7	5	NM_001040167.2	ENSP00000222725.5

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 9516 AN: 152042 Hom.: 426 Cov.: 32

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.00213

Gnomad SAS AF: 0.0265

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0878

Gnomad OTH AF: 0.0645

GnomAD2 exomes AF: 0.0702 AC: 16906 AN: 240754 AF XY: 0.0680

Gnomad AFR exome AF: 0.0144

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.0576

Gnomad EAS exome AF: 0.00134

Gnomad FIN exome AF: 0.0596

Gnomad NFE exome AF: 0.0852

Gnomad OTH exome AF: 0.0719

GnomAD4 exome AF: 0.0826 AC: 119501 AN: 1446810 Hom.: 5518 Cov.: 30 AF XY: 0.0809 AC XY: 58293 AN XY: 720466

African (AFR) AF: 0.0136 AC: 452 AN: 33184

American (AMR) AF: 0.128 AC: 5681 AN: 44450

Ashkenazi Jewish (ASJ) AF: 0.0560 AC: 1453 AN: 25946

East Asian (EAS) AF: 0.000936 AC: 37 AN: 39542

South Asian (SAS) AF: 0.0303 AC: 2593 AN: 85692

European-Finnish (FIN) AF: 0.0594 AC: 3083 AN: 51876

Middle Eastern (MID) AF: 0.0306 AC: 175 AN: 5712

European-Non Finnish (NFE) AF: 0.0925 AC: 101805 AN: 1100564

Other (OTH) AF: 0.0706 AC: 4222 AN: 59844

GnomAD4 genome AF: 0.0626 AC: 9529 AN: 152162 Hom.: 428 Cov.: 32 AF XY: 0.0605 AC XY: 4499 AN XY: 74400

African (AFR) AF: 0.0180 AC: 747 AN: 41528

American (AMR) AF: 0.110 AC: 1680 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 215 AN: 3468

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5152

South Asian (SAS) AF: 0.0263 AC: 127 AN: 4828

European-Finnish (FIN) AF: 0.0535 AC: 568 AN: 10608

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0878 AC: 5968 AN: 67962

Other (OTH) AF: 0.0648 AC: 137 AN: 2114

Alfa AF: 0.0754 Hom.: 104

Bravo AF: 0.0647

Asia WGS AF: 0.0230 AC: 80 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Aug 31, 2019

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	-0.86
CADD	Benign	5.9
DANN	Benign	0.73
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs13225716; hg19: chr7-2566433;