15-38253072-G-C

Variant names:

• chr15-38253072-G-C
• rs1489810093
• NM_152594.3:c.-114G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_152594.3(SPRED1):​c.-114G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 720,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SPRED1 NM_152594.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 0 publications found

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]

SPRED1 Gene-Disease associations (from GenCC):

• Legius syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Genomics England PanelApp, ClinGen, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000310144 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRED1	NM_152594.3	c.-114G>C		5_prime_UTR_variant	Exon 1 of 7	ENST00000299084.9	NP_689807.1
SPRED1	XM_005254202.4	c.-114G>C		5_prime_UTR_variant	Exon 1 of 8		XP_005254259.1
SPRED1	XM_047432199.1	c.-277G>C		5_prime_UTR_variant	Exon 1 of 9		XP_047288155.1
SPRED1	XM_047432200.1	c.-241G>C		5_prime_UTR_variant	Exon 1 of 8		XP_047288156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRED1	ENST00000299084.9	c.-114G>C		5_prime_UTR_variant	Exon 1 of 7	1	NM_152594.3	ENSP00000299084.4
SPRED1	ENST00000561205.1	n.225G>C		non_coding_transcript_exon_variant	Exon 1 of 5	5
ENSG00000310144	ENST00000847565.1	n.95+495C>G		intron_variant	Intron 1 of 1
SPRED1	ENST00000561317.1	c.-241G>C		upstream_gene_variant		4		ENSP00000453680.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000139 AC: 10 AN: 720044 Hom.: 0 Cov.: 9 AF XY: 0.0000185 AC XY: 7 AN XY: 378936

African (AFR) AF: 0.00 AC: 0 AN: 18604

American (AMR) AF: 0.00 AC: 0 AN: 34774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20794

East Asian (EAS) AF: 0.00 AC: 0 AN: 32628

South Asian (SAS) AF: 0.000152 AC: 10 AN: 65862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3194

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 468578

Other (OTH) AF: 0.00 AC: 0 AN: 35670

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Benign	0.92
PhyloP100		1.4
PromoterAI		-0.060	Neutral

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

Other links and lift over

dbSNP: rs1489810093; hg19: chr15-38545273;