15-38253034-C-T

Variant names:

• chr15-38253034-C-T
• rs886051102
• NM_152594.3:c.-152C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_152594.3(SPRED1):​c.-152C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000805 in 708,472 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: 𝑓 0.000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000084 (0 hom.)
• Consequence: SPRED1 NM_152594.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• 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: PanelApp Australia, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P

ENSG00000310144 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000659 (10/151698) while in subpopulation AMR AF = 0.000655 (10/15264). AF 95% confidence interval is 0.000355. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152594.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRED1	NM_152594.3	MANE Select	c.-152C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_689807.1	Q7Z699
	SPRED1	NM_152594.3	MANE Select	c.-152C>T		5_prime_UTR	Exon 1 of 7	NP_689807.1	Q7Z699

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRED1	ENST00000299084.9	TSL:1 MANE Select	c.-152C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000299084.4	Q7Z699
	SPRED1	ENST00000299084.9	TSL:1 MANE Select	c.-152C>T		5_prime_UTR	Exon 1 of 7	ENSP00000299084.4	Q7Z699
	SPRED1	ENST00000881380.1		c.-152C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000551439.1

Frequencies

GnomAD3 genomes AF: 0.0000659 AC: 10 AN: 151698 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000844 AC: 47 AN: 556774 Hom.: 0 Cov.: 6 AF XY: 0.0000536 AC XY: 16 AN XY: 298314

African (AFR) AF: 0.00 AC: 0 AN: 15574

American (AMR) AF: 0.00136 AC: 45 AN: 33092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18852

East Asian (EAS) AF: 0.0000315 AC: 1 AN: 31744

South Asian (SAS) AF: 0.00 AC: 0 AN: 60788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2408

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 330162

Other (OTH) AF: 0.0000331 AC: 1 AN: 30196

GnomAD4 genome AF: 0.0000659 AC: 10 AN: 151698 Hom.: 0 Cov.: 31 AF XY: 0.0000540 AC XY: 4 AN XY: 74038

African (AFR) AF: 0.00 AC: 0 AN: 41292

American (AMR) AF: 0.000655 AC: 10 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5074

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67882

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	22
DANN	Benign	0.92
PhyloP100		2.0
PromoterAI		-0.0052	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs886051102; hg19: chr15-38545235;