8-89947815-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002485.5(NBN):c.1914+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,521,356 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_002485.5 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0174 AC: 2648AN: 151938Hom.: 76 Cov.: 32
GnomAD3 exomes AF: 0.00388 AC: 861AN: 221874Hom.: 30 AF XY: 0.00273 AC XY: 327AN XY: 119806
GnomAD4 exome AF: 0.00169 AC: 2317AN: 1369300Hom.: 45 Cov.: 23 AF XY: 0.00148 AC XY: 1009AN XY: 683760
GnomAD4 genome AF: 0.0176 AC: 2669AN: 152056Hom.: 77 Cov.: 32 AF XY: 0.0172 AC XY: 1282AN XY: 74362
ClinVar
Submissions by phenotype
not specified Benign:4
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Microcephaly, normal intelligence and immunodeficiency Benign:4
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
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not provided Benign:2
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Hereditary cancer-predisposing syndrome Benign:2
This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
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Acute lymphoid leukemia Benign:1
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Malignant tumor of breast Benign:1
The NBN c.1914+9C>T variant was not identified in the literature nor was it identified in the Cosmic, LOVD 3.0, and Zhejiang Colon Cancer Database. The variant was identified in dbSNP (ID: rs13312938) “With other allele”, ClinVar (benign by Invitae and Ambry Genetics, and likely benign by Illumina), Clinvitae (2x), and in control databases in 1353 (42 homozygous) of 246988 chromosomes at a frequency of 0.005 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017), being identified in the following populations: African in 1230 (41 homozygous) of 21232 chromosomes (frequency: 0.06), Other in 19 of 5832 chromosomes (frequency: 003), Latino in 82 of 32908 chromosomes (frequency: 0.002), European Non-Finnish in 13 of 108340 chromosomes (frequency: 0.0001), East Asian in 1 of 17718 chromosomes (frequency: 0.00006), South Asian in 8 (1 homozygous) of 27888 chromosomes (frequency: 0.0003). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. -
Hereditary breast ovarian cancer syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at