dbSNP rs7163339: SPRED1:c.424-98T>C (chr15-38339639-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.96

Publications

5 publications found

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 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)

SPRED1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.424-98T>C		intron_variant	Intron 4 of 6	ENST00000299084.9	NP_689807.1	Q7Z699

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRED1	ENST00000299084.9 link	c.424-98T>C		intron_variant	Intron 4 of 6	1	NM_152594.3	ENSP00000299084.4		Q7Z699
SPRED1	ENST00000561317.1 link	c.361-98T>C		intron_variant	Intron 5 of 5	4		ENSP00000453680.1		H0YMN8

Frequencies

GnomAD3 genomes

AF:

0.824

AC:

125276

AN:

152006

Hom.:

52425

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

5143

10286

15428

20571

25714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13396

26792

40188

53584

66980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.824

AC:

125340

AN:

152124

Hom.:

52438

Cov.:

AF XY:

0.826

AC XY:

61412

AN XY:

74376

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1090

2181

3271

4362

5452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

LINK: link

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

(source)

DANN

Benign

0.51

PhyloP100

-3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over