8-89984571-T-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_002485.5(NBN):c.-10A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,612,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_002485.5 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NBN | NM_002485.5 | c.-10A>T | 5_prime_UTR_variant | Exon 1 of 16 | ENST00000265433.8 | NP_002476.2 | ||
NBN | NM_001024688.3 | c.-306A>T | 5_prime_UTR_variant | Exon 1 of 17 | NP_001019859.1 | |||
NBN | XM_011517046.2 | c.-10A>T | 5_prime_UTR_variant | Exon 1 of 11 | XP_011515348.1 | |||
NBN | XM_047421796.1 | c.-10A>T | 5_prime_UTR_variant | Exon 1 of 10 | XP_047277752.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000246 AC: 6AN: 244114Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133506
GnomAD4 exome AF: 0.0000507 AC: 74AN: 1460576Hom.: 0 Cov.: 30 AF XY: 0.0000399 AC XY: 29AN XY: 726648
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74360
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
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Variant summary: The NBN c.-10A>T variant involves the alteration of a non-conserved nucleotide in the 5 region. One in silico tool predicts a benign outcome for this variant. 3/5 splice prediction tools predict a gain of cryptic splicing donor site. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1/109698 control chromosomes at a frequency of 0.0000091, which does not exceed the estimated maximal expected allele frequency of a pathogenic NBN variant (0.0025). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available. -
NBN-related disorder Uncertain:1
The NBN c.-10A>T variant is located in the 5' untranslated region. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0048% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-90996799-T-A). In ClinVar, this variant is interpreted as benign/likely benign/uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/492068/?new_evidence=false). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Microcephaly, normal intelligence and immunodeficiency Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at