15-38253023-TG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_152594.3(SPRED1):c.-156del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 671,690 control chromosomes in the GnomAD database, including 27 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (7 hom., cov: 31)
  • Exomes 𝑓: 0.0018 (20 hom.)
• Consequence: SPRED1 NM_152594.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.24

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-38253023-TG-T is Benign according to our data. Variant chr15-38253023-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 315729.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0023 (349/151676) while in subpopulation AMR AF= 0.0218 (333/15262). AF 95% confidence interval is 0.0199. There are 7 homozygotes in gnomad4. There are 206 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 349 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPRED1	NM_152594.3	c.-156del		5_prime_UTR_variant	1/7	ENST00000299084.9
SPRED1	XM_005254202.4	c.-156del		5_prime_UTR_variant	1/8
SPRED1	XM_047432199.1	c.-319del		5_prime_UTR_variant	1/9
SPRED1	XM_047432200.1	c.-283del		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPRED1	ENST00000299084.9	c.-156del		5_prime_UTR_variant	1/7	1	NM_152594.3	P1
SPRED1	ENST00000561205.1	n.183del		non_coding_transcript_exon_variant	1/5	5

Frequencies

GnomAD3 genomes AF: 0.00230 AC: 349 AN: 151560 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0218

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: 0.0000147

Gnomad OTH AF: 0.00432

GnomAD4 exome AF: 0.00179 AC: 929 AN: 520014 Hom.: 20 Cov.: 6 AF XY: 0.00143 AC XY: 398 AN XY: 277798

Gnomad4 AFR exome AF: 0.000136

Gnomad4 AMR exome AF: 0.0295

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000953

Gnomad4 SAS exome AF: 0.0000354

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000519

Gnomad4 OTH exome AF: 0.00188

GnomAD4 genome AF: 0.00230 AC: 349 AN: 151676 Hom.: 7 Cov.: 31 AF XY: 0.00278 AC XY: 206 AN XY: 74154

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.0218

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00427

Bravo AF: 0.00339

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Legius syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs531519324; hg19: chr15-38545224;