15-38339639-T-G

Variant names:

• chr15-38339639-T-G
• rs7163339
• NM_152594.3:c.424-98T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152594.3(SPRED1):​c.424-98T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPRED1 NM_152594.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96
• Publications: 5 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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRED1	NM_152594.3	c.424-98T>G		intron_variant	Intron 4 of 6	ENST00000299084.9	NP_689807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRED1	ENST00000299084.9	c.424-98T>G		intron_variant	Intron 4 of 6	1	NM_152594.3	ENSP00000299084.4
SPRED1	ENST00000561317.1	c.361-98T>G		intron_variant	Intron 5 of 5	4		ENSP00000453680.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000178 AC: 2 AN: 1125700 Hom.: 0 AF XY: 0.00000173 AC XY: 1 AN XY: 576654

African (AFR) AF: 0.00 AC: 0 AN: 27458

American (AMR) AF: 0.00 AC: 0 AN: 43718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23764

East Asian (EAS) AF: 0.0000525 AC: 2 AN: 38128

South Asian (SAS) AF: 0.00 AC: 0 AN: 78716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5132

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 811250

Other (OTH) AF: 0.00 AC: 0 AN: 49440

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.027
DANN	Benign	0.47
PhyloP100		-3.0

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

Other links and lift over

dbSNP: rs7163339; hg19: chr15-38631840;