rs150681693
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBS1_SupportingBS2
The NM_002334.4(LRP4):c.3944C>T(p.Ser1315Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000768 in 1,613,310 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S1315S) has been classified as Likely benign.
Frequency
Consequence
NM_002334.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRP4 | NM_002334.4 | c.3944C>T | p.Ser1315Leu | missense_variant | 28/38 | ENST00000378623.6 | |
LRP4 | XM_017017734.2 | c.3944C>T | p.Ser1315Leu | missense_variant | 28/39 | ||
LRP4 | XM_011520103.3 | c.3140C>T | p.Ser1047Leu | missense_variant | 22/32 | ||
LRP4 | XM_011520104.3 | c.1709C>T | p.Ser570Leu | missense_variant | 13/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRP4 | ENST00000378623.6 | c.3944C>T | p.Ser1315Leu | missense_variant | 28/38 | 1 | NM_002334.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000453 AC: 69AN: 152176Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000451 AC: 113AN: 250556Hom.: 1 AF XY: 0.000465 AC XY: 63AN XY: 135510
GnomAD4 exome AF: 0.000801 AC: 1170AN: 1461016Hom.: 6 Cov.: 32 AF XY: 0.000780 AC XY: 567AN XY: 726854
GnomAD4 genome ? AF: 0.000453 AC: 69AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34AN XY: 74476
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 16, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 27, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 12, 2023 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 14, 2017 | - - |
Cenani-Lenz syndactyly syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 16, 2021 | The c.3944C>T (p.S1315L) alteration is located in exon 28 (coding exon 28) of the LRP4 gene. This alteration results from a C to T substitution at nucleotide position 3944, causing the serine (S) at amino acid position 1315 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Cenani-Lenz syndactyly syndrome;C3280402:Sclerosteosis 2;C4225377:Congenital myasthenic syndrome 17 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at