rs4253526
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_005411.5(SFTPA1):āc.552T>Cā(p.Tyr184Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 1,613,958 control chromosomes in the GnomAD database, including 1,927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.025 ( 239 hom., cov: 32)
Exomes š: 0.018 ( 1688 hom. )
Consequence
SFTPA1
NM_005411.5 synonymous
NM_005411.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.97
Genes affected
SFTPA1 (HGNC:10798): (surfactant protein A1) This gene encodes a lung surfactant protein that is a member of a subfamily of C-type lectins called collectins. The encoded protein binds specific carbohydrate moieties found on lipids and on the surface of microorganisms. This protein plays an essential role in surfactant homeostasis and in the defense against respiratory pathogens. Mutations in this gene are associated with idiopathic pulmonary fibrosis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 10-79613918-T-C is Benign according to our data. Variant chr10-79613918-T-C is described in ClinVar as [Benign]. Clinvar id is 165200.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SFTPA1 | NM_005411.5 | c.552T>C | p.Tyr184Tyr | synonymous_variant | 6/6 | ENST00000398636.8 | NP_005402.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SFTPA1 | ENST00000398636.8 | c.552T>C | p.Tyr184Tyr | synonymous_variant | 6/6 | 1 | NM_005411.5 | ENSP00000381633.3 | ||
SFTPA1 | ENST00000419470.6 | c.597T>C | p.Tyr199Tyr | synonymous_variant | 6/6 | 1 | ENSP00000397082.2 | |||
SFTPA1 | ENST00000428376.6 | c.552T>C | p.Tyr184Tyr | synonymous_variant | 5/5 | 1 | ENSP00000411102.2 |
Frequencies
GnomAD3 genomes AF: 0.0251 AC: 3823AN: 152174Hom.: 237 Cov.: 32
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GnomAD3 exomes AF: 0.0422 AC: 10604AN: 251200Hom.: 868 AF XY: 0.0415 AC XY: 5636AN XY: 135768
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GnomAD4 exome AF: 0.0182 AC: 26551AN: 1461666Hom.: 1688 Cov.: 33 AF XY: 0.0195 AC XY: 14155AN XY: 727146
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GnomAD4 genome AF: 0.0251 AC: 3828AN: 152292Hom.: 239 Cov.: 32 AF XY: 0.0275 AC XY: 2050AN XY: 74464
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Tyr199Tyr in exon 6 of SFTPA1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 2.6% (115/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs148138544). - |
SFTPA1-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 17, 2024 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at