rs182465294
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001098668.4(SFTPA2):c.292+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00456 in 1,613,858 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0099 ( 12 hom., cov: 32)
Exomes 𝑓: 0.0040 ( 32 hom. )
Consequence
SFTPA2
NM_001098668.4 intron
NM_001098668.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.633
Genes affected
SFTPA2 (HGNC:10799): (surfactant protein A2) This gene is one of several genes encoding pulmonary-surfactant associated proteins (SFTPA) located on chromosome 10. Mutations in this gene and a highly similar gene located nearby, which affect the highly conserved carbohydrate recognition domain, are associated with idiopathic pulmonary fibrosis. The current version of the assembly displays only a single centromeric SFTPA gene pair rather than the two gene pairs shown in the previous assembly which were thought to have resulted from a duplication. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 10-79558875-G-A is Benign according to our data. Variant chr10-79558875-G-A is described in ClinVar as [Benign]. Clinvar id is 227068.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00986 (1499/152050) while in subpopulation AFR AF= 0.0252 (1046/41454). AF 95% confidence interval is 0.024. There are 12 homozygotes in gnomad4. There are 715 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1488 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SFTPA2 | NM_001098668.4 | c.292+11C>T | intron_variant | ENST00000372325.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SFTPA2 | ENST00000372325.7 | c.292+11C>T | intron_variant | 1 | NM_001098668.4 | P1 | |||
SFTPA2 | ENST00000372327.9 | c.292+11C>T | intron_variant | 1 | P1 | ||||
SFTPA2 | ENST00000417041.1 | c.292+11C>T | intron_variant | 5 | |||||
SFTPA2 | ENST00000492049.1 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00979 AC: 1488AN: 151932Hom.: 12 Cov.: 32
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GnomAD3 exomes AF: 0.00557 AC: 1401AN: 251330Hom.: 6 AF XY: 0.00549 AC XY: 746AN XY: 135846
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GnomAD4 exome AF: 0.00401 AC: 5860AN: 1461808Hom.: 32 Cov.: 70 AF XY: 0.00419 AC XY: 3050AN XY: 727206
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GnomAD4 genome ? AF: 0.00986 AC: 1499AN: 152050Hom.: 12 Cov.: 32 AF XY: 0.00962 AC XY: 715AN XY: 74356
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 16, 2016 | c.292+11C>T in intron 4 of SFTPA2: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence. I t has been identified in 2.7% (278/10396) of African chromosomes including 2 hom ozygotes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs182465294). - |
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