rs727504717
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_152594.3(SPRED1):c.27C>T(p.Asp9=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000019 in 1,578,396 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SPRED1
NM_152594.3 synonymous
NM_152594.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 5.00
Genes affected
SPRED1 (HGNC:20249): (sprouty related EVH1 domain containing 1) The protein encoded by this gene is a member of the Sprouty family of proteins and is phosphorylated by tyrosine kinase in response to several growth factors. The encoded protein can act as a homodimer or as a heterodimer with SPRED2 to regulate activation of the MAP kinase cascade. Defects in this gene are a cause of neurofibromatosis type 1-like syndrome (NFLS). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
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Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 15-38253212-C-T is Benign according to our data. Variant chr15-38253212-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 179219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPRED1 | NM_152594.3 | c.27C>T | p.Asp9= | synonymous_variant | 1/7 | ENST00000299084.9 | |
SPRED1 | XM_005254202.4 | c.27C>T | p.Asp9= | synonymous_variant | 1/8 | ||
SPRED1 | XM_047432199.1 | c.-137C>T | 5_prime_UTR_variant | 1/9 | |||
SPRED1 | XM_047432200.1 | c.-101C>T | 5_prime_UTR_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPRED1 | ENST00000299084.9 | c.27C>T | p.Asp9= | synonymous_variant | 1/7 | 1 | NM_152594.3 | P1 | |
SPRED1 | ENST00000561317.1 | c.-101C>T | 5_prime_UTR_variant | 1/6 | 4 | ||||
SPRED1 | ENST00000561205.1 | n.365C>T | non_coding_transcript_exon_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000511 AC: 1AN: 195744Hom.: 0 AF XY: 0.00000958 AC XY: 1AN XY: 104350
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GnomAD4 exome AF: 0.00000140 AC: 2AN: 1426236Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1AN XY: 705906
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 06, 2013 | Asp9Asp in exon 1 of SPRED1: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. - |
Legius syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 04, 2023 | - - |
Computational scores
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Name
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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