rs35910969
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004252.5(NHERF1):āc.328C>Gā(p.Leu110Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 1,533,822 control chromosomes in the GnomAD database, including 619 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Consequence
NM_004252.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NHERF1 | ENST00000262613.10 | c.328C>G | p.Leu110Val | missense_variant | Exon 1 of 6 | 1 | NM_004252.5 | ENSP00000262613.5 | ||
NHERF1 | ENST00000583369.5 | c.328C>G | p.Leu110Val | missense_variant | Exon 1 of 3 | 3 | ENSP00000464321.1 |
Frequencies
GnomAD3 genomes AF: 0.0162 AC: 2460AN: 152030Hom.: 33 Cov.: 32
GnomAD3 exomes AF: 0.0148 AC: 1929AN: 130476Hom.: 20 AF XY: 0.0146 AC XY: 1049AN XY: 71744
GnomAD4 exome AF: 0.0263 AC: 36341AN: 1381674Hom.: 586 Cov.: 32 AF XY: 0.0254 AC XY: 17319AN XY: 680916
GnomAD4 genome AF: 0.0162 AC: 2460AN: 152148Hom.: 33 Cov.: 32 AF XY: 0.0150 AC XY: 1119AN XY: 74402
ClinVar
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 15, 2019 | This variant is associated with the following publications: (PMID: 31672324, 18784102, 26787776, 25333069, 22995991, 31171716, 29275531) - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 03, 2025 | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2024 | NHERF1: BS1, BS2 - |
Hypophosphatemic nephrolithiasis/osteoporosis 2 Pathogenic:1Benign:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 11, 2008 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | Feb 04, 2025 | Variant NM_004252.5(NHERF1):c.328C>G (p.Leu110Val) is an old submission that was updated given new versions of GnomAD. It has GnomAD 4.1.0 frequency of 0.02530 with 619 homozygotes. It was found internally in patients with different phenotypes explained by other variants. Applied assertion criteria redefined it as Benign. - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at