chr15-38253011-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152594.3(SPRED1):​c.-175G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 486,188 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SPRED1
NM_152594.3 5_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.879
Variant links:
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SPRED1NM_152594.3 linkuse as main transcriptc.-175G>T 5_prime_UTR_variant 1/7 ENST00000299084.9
SPRED1XM_005254202.4 linkuse as main transcriptc.-175G>T 5_prime_UTR_variant 1/8
SPRED1XM_047432199.1 linkuse as main transcriptc.-338G>T 5_prime_UTR_variant 1/9
SPRED1XM_047432200.1 linkuse as main transcriptc.-302G>T 5_prime_UTR_variant 1/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SPRED1ENST00000299084.9 linkuse as main transcriptc.-175G>T 5_prime_UTR_variant 1/71 NM_152594.3 P1
SPRED1ENST00000561205.1 linkuse as main transcriptn.164G>T non_coding_transcript_exon_variant 1/55

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000206
AC:
1
AN:
486188
Hom.:
0
Cov.:
5
AF XY:
0.00
AC XY:
0
AN XY:
259276
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000345
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Legius syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 15, 2018This 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
CADD
Benign
19
DANN
Benign
0.96
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1312214893; hg19: chr15-38545212; API