rs7163339

Positions:

• chr15-38339639-T-C
• chr15-38339639-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152594.3(SPRED1):​c.424-98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 1,275,682 control chromosomes in the GnomAD database, including 488,506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.82 (52438 hom., cov: 32)
  • Exomes 𝑓: 0.88 (436068 hom.)
• Consequence: SPRED1 NM_152594.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.96

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-38339639-T-C is Benign according to our data. Variant chr15-38339639-T-C is described in ClinVar as [Benign]. Clinvar id is 561406.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPRED1	NM_152594.3	c.424-98T>C		intron_variant		ENST00000299084.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPRED1	ENST00000299084.9	c.424-98T>C		intron_variant		1	NM_152594.3	P1
SPRED1	ENST00000561317.1	c.361-98T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125276 AN: 152006 Hom.: 52425 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.830

GnomAD4 exome AF: 0.880 AC: 988172 AN: 1123558 Hom.: 436068 AF XY: 0.882 AC XY: 507554 AN XY: 575684

Gnomad4 AFR exome AF: 0.632

Gnomad4 AMR exome AF: 0.832

Gnomad4 ASJ exome AF: 0.905

Gnomad4 EAS exome AF: 0.782

Gnomad4 SAS exome AF: 0.891

Gnomad4 FIN exome AF: 0.932

Gnomad4 NFE exome AF: 0.891

Gnomad4 OTH exome AF: 0.867

GnomAD4 genome AF: 0.824 AC: 125340 AN: 152124 Hom.: 52438 Cov.: 32 AF XY: 0.826 AC XY: 61412 AN XY: 74376

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.842

Gnomad4 ASJ AF: 0.901

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.878

Gnomad4 FIN AF: 0.934

Gnomad4 NFE AF: 0.897

Gnomad4 OTH AF: 0.823

Alfa AF: 0.850 Hom.: 8101

Bravo AF: 0.805

Asia WGS AF: 0.795 AC: 2763 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.034
DANN	Benign	0.51

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: rs7163339; hg19: chr15-38631840;