15-38252854-G-A

Variant names:

• chr15-38252854-G-A
• rs147075186
• NM_152594.3:c.-332G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_152594.3(SPRED1):​c.-332G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 419,478 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0067 (5 hom., cov: 31)
  • Exomes 𝑓: 0.00074 (1 hom.)
• Consequence: SPRED1 NM_152594.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0970
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-38252854-G-A is Benign according to our data. Variant chr15-38252854-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1216131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00667 (1016/152238) while in subpopulation AFR AF = 0.023 (954/41552). AF 95% confidence interval is 0.0217. There are 5 homozygotes in GnomAd4. There are 464 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1016 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRED1	NM_152594.3	c.-332G>A		5_prime_UTR_variant	Exon 1 of 7	ENST00000299084.9	NP_689807.1
SPRED1	XM_005254202.4	c.-332G>A		5_prime_UTR_variant	Exon 1 of 8		XP_005254259.1
SPRED1	XM_047432199.1	c.-495G>A		5_prime_UTR_variant	Exon 1 of 9		XP_047288155.1
SPRED1	XM_047432200.1	c.-459G>A		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.-332G>A		5_prime_UTR_variant	Exon 1 of 7	1	NM_152594.3	ENSP00000299084.4
SPRED1	ENST00000561205.1	n.7G>A		non_coding_transcript_exon_variant	Exon 1 of 5	5
ENSG00000310144	ENST00000847565.1	n.95+713C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00667 AC: 1015 AN: 152126 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

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: 0.0000441

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.000737 AC: 197 AN: 267240 Hom.: 1 Cov.: 0 AF XY: 0.000630 AC XY: 90 AN XY: 142780

African (AFR) AF: 0.0219 AC: 150 AN: 6840

American (AMR) AF: 0.00122 AC: 15 AN: 12280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7414

East Asian (EAS) AF: 0.00 AC: 0 AN: 14670

South Asian (SAS) AF: 0.0000518 AC: 2 AN: 38646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14190

Middle Eastern (MID) AF: 0.00183 AC: 2 AN: 1092

European-Non Finnish (NFE) AF: 0.0000572 AC: 9 AN: 157326

Other (OTH) AF: 0.00129 AC: 19 AN: 14782

GnomAD4 genome AF: 0.00667 AC: 1016 AN: 152238 Hom.: 5 Cov.: 31 AF XY: 0.00623 AC XY: 464 AN XY: 74456

African (AFR) AF: 0.0230 AC: 954 AN: 41552

American (AMR) AF: 0.00327 AC: 50 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67978

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00576 Hom.: 0

Bravo AF: 0.00803

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		-0.097
PromoterAI		-0.057	Neutral
Mutation Taster		=300/0	polymorphism

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: rs147075186; hg19: chr15-38545055;