chr2-85667185-G-T
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000542.5(SFTPB):c.196-8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,606,802 control chromosomes in the GnomAD database, including 106,754 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000542.5 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Our verdict: Benign. The variant received -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.301 AC: 45785AN: 151932Hom.: 8087 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.361 AC: 90187AN: 249836 AF XY: 0.367 show subpopulations
GnomAD4 exome AF: 0.363 AC: 528395AN: 1454752Hom.: 98667 Cov.: 33 AF XY: 0.366 AC XY: 265263AN XY: 723956 show subpopulations
GnomAD4 genome AF: 0.301 AC: 45789AN: 152050Hom.: 8087 Cov.: 32 AF XY: 0.301 AC XY: 22406AN XY: 74320 show subpopulations
ClinVar
Submissions by phenotype
not provided Benign:3
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not specified Benign:2
232-8C>A in intron 3 of SFTPB: This variant is not expected to have clinical sig nificance because it has been identified in 37.5% (3227/8600) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs3024798). -
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Surfactant metabolism dysfunction, pulmonary, 1 Benign:2
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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. -
Hereditary pulmonary alveolar proteinosis Benign:1
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at