rs61732310
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_006179.5(NTF4):c.263C>T(p.Ala88Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 1,611,310 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0025 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0034 ( 38 hom. )
Consequence
NTF4
NM_006179.5 missense
NM_006179.5 missense
Scores
2
13
Clinical Significance
Conservation
PhyloP100: 1.65
Genes affected
NTF4 (HGNC:8024): (neurotrophin 4) This gene is a member of a family of neurotrophic factors, neurotrophins, that control survival and differentiation of mammalian neurons. The expression of this gene is ubiquitous and less influenced by environmental signals. While knock-outs of other neurotrophins including nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 prove lethal during early postnatal development, NTF5-deficient mice only show minor cellular deficits and develop normally to adulthood. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP6
?
Variant 19-49061735-G-A is Benign according to our data. Variant chr19-49061735-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 14017.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00253 (386/152332) while in subpopulation SAS AF= 0.0189 (91/4824). AF 95% confidence interval is 0.0157. There are 3 homozygotes in gnomad4. There are 196 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 388 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NTF4 | NM_006179.5 | c.263C>T | p.Ala88Val | missense_variant | 2/2 | ENST00000593537.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NTF4 | ENST00000593537.2 | c.263C>T | p.Ala88Val | missense_variant | 2/2 | NM_006179.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00255 AC: 388AN: 152214Hom.: 3 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00454 AC: 1093AN: 240822Hom.: 11 AF XY: 0.00536 AC XY: 705AN XY: 131522
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GnomAD4 exome AF: 0.00343 AC: 4998AN: 1458978Hom.: 38 Cov.: 32 AF XY: 0.00391 AC XY: 2836AN XY: 725736
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GnomAD4 genome ? AF: 0.00253 AC: 386AN: 152332Hom.: 3 Cov.: 32 AF XY: 0.00263 AC XY: 196AN XY: 74492
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3478
ClinVar
Significance: Likely benign
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Glaucoma 1, open angle, O Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | OMIM | Mar 12, 2010 | - - |
Intellectual disability, X-linked 99 Benign:1
Likely benign, criteria provided, single submitter | research | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | - | The heterozygous p.Ala88Val variant in NTF4 has been identified in at least 13 individuals with glaucoma and at least 19 individuals without glaucoma (PMID: 19765683, 20215012, 20463313), but has also been identified in >2% of South Asian chromosomes and 8 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for autosomal dominant primary open angle glaucoma. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
A
PrimateAI
Uncertain
T
Sift4G
Benign
T;.
Polyphen
D;.
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at