chr15-38339639-T-C

Variant names:

• chr15-38339639-T-C
• rs7163339
• NM_152594.3:c.424-98T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.96
• Publications: 5 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)

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 561406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SPRED1	NM_152594.3	c.424-98T>C		intron_variant	Intron 4 of 6	ENST00000299084.9	NP_689807.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRED1	ENST00000299084.9	c.424-98T>C		intron_variant	Intron 4 of 6	1	NM_152594.3	ENSP00000299084.4
SPRED1	ENST00000561317.1	c.361-98T>C		intron_variant	Intron 5 of 5	4		ENSP00000453680.1

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

African (AFR) AF: 0.632 AC: 17306 AN: 27364

American (AMR) AF: 0.832 AC: 36314 AN: 43670

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 21491 AN: 23734

East Asian (EAS) AF: 0.782 AC: 29820 AN: 38110

South Asian (SAS) AF: 0.891 AC: 70059 AN: 78632

European-Finnish (FIN) AF: 0.932 AC: 44789 AN: 48070

Middle Eastern (MID) AF: 0.835 AC: 4278 AN: 5124

European-Non Finnish (NFE) AF: 0.891 AC: 721303 AN: 809494

Other (OTH) AF: 0.867 AC: 42812 AN: 49360

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

African (AFR) AF: 0.663 AC: 27500 AN: 41472

American (AMR) AF: 0.842 AC: 12849 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3130 AN: 3472

East Asian (EAS) AF: 0.792 AC: 4099 AN: 5176

South Asian (SAS) AF: 0.878 AC: 4229 AN: 4816

European-Finnish (FIN) AF: 0.934 AC: 9904 AN: 10608

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.897 AC: 60968 AN: 68000

Other (OTH) AF: 0.823 AC: 1736 AN: 2110

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs7163339; hg19: chr15-38631840;