Variant rs7179118 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152594.3(SPRED1):c.424-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,610,272 control chromosomes in the GnomAD database, including 49,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.23 ( 4372 hom., cov: 32)

Exomes 𝑓: 0.24 ( 45346 hom. )

Consequence

SPRED1
NM_152594.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.0500

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 15-38339719-G-A is Benign according to our data. Variant chr15-38339719-G-A is described in ClinVar as [Benign]. Clinvar id is 41452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-38339719-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRED1	NM_152594.3 linkuse as main transcript	c.424-18G>A		intron_variant		ENST00000299084.9	NP_689807.1	Q7Z699

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPRED1	ENST00000299084.9 linkuse as main transcript	c.424-18G>A		intron_variant		1	NM_152594.3	ENSP00000299084.4		Q7Z699
SPRED1	ENST00000561317.1 linkuse as main transcript	c.361-18G>A		intron_variant		4		ENSP00000453680.1		H0YMN8

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35643

AN:

151874

Hom.:

4372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.243

Gnomad EAS

AF:

0.0326

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.244

GnomAD3 exomes

AF:

0.223

AC:

56008

AN:

250910

Hom.:

6888

AF XY:

0.226

AC XY:

30602

AN XY:

135646

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.179

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.0313

Gnomad SAS exome

AF:

0.174

Gnomad FIN exome

AF:

0.285

Gnomad NFE exome

AF:

0.265

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.244

AC:

356131

AN:

1458280

Hom.:

45346

Cov.:

AF XY:

0.243

AC XY:

176195

AN XY:

725568

show subpopulations

Gnomad4 AFR exome

AF:

0.222

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.0478

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.283

Gnomad4 NFE exome

AF:

0.258

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.235

AC:

35655

AN:

151992

Hom.:

4372

Cov.:

AF XY:

0.231

AC XY:

17200

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.229

Gnomad4 AMR

AF:

0.193

Gnomad4 ASJ

AF:

0.243

Gnomad4 EAS

AF:

0.0327

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.281

Gnomad4 NFE

AF:

0.260

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.254

Hom.:

868

Bravo

AF:

0.229

Asia WGS

AF:

0.104

AC:

359

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 10, 2015	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 15, 2015	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. -

Legius syndrome

Benign:5

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 17, 2017	Variant summary: The SPRED1 c.424-18G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing and ESE finder predicts no impact on ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC at a frequency of 0.2265353 (27452/121182 control chromosomes [3368 homozygotes]), which is approximately 90614 times the estimated maximal expected allele frequency of a pathogenic SPRED1 variant (0.0000025), providing very strong evidence that this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. To our knowledge, the variant of interest has not been reported in affected individuals via publications, nor has it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.67

BranchPoint Hunter

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over