Genetic Variant SPRED1:c.-156delG (chr15-38253023-TG-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_152594.3(SPRED1):c.-156delG 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

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.24

Publications

0 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: ClinGen, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, PanelApp Australia

SPRED1 links:

ENSG00000310144 (HGNC:):

ENSG00000310144 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 349 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152594.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRED1	NM_152594.3	MANE Select	c.-156delG		5_prime_UTR	Exon 1 of 7	NP_689807.1	Q7Z699

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SPRED1	ENST00000299084.9	TSL:1 MANE Select	c.-156delG	5_prime_UTR	Exon 1 of 7	ENSP00000299084.4	Q7Z699
SPRED1	ENST00000881380.1		c.-156delG	5_prime_UTR	Exon 1 of 8	ENSP00000551439.1
SPRED1	ENST00000951939.1		c.-156delG	5_prime_UTR	Exon 1 of 8	ENSP00000621998.1

Frequencies

GnomAD3 genomes

AF:

0.00230

AC:

349

AN:

151560

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00143

AC XY:

398

AN XY:

277798

show subpopulations

African (AFR)

AF:

0.000136

AC:

AN:

14722

American (AMR)

AF:

0.0295

AC:

852

AN:

28908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17170

East Asian (EAS)

AF:

0.0000953

AC:

AN:

31478

South Asian (SAS)

AF:

0.0000354

AC:

AN:

56432

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2248

European-Non Finnish (NFE)

AF:

0.0000519

AC:

AN:

308142

Other (OTH)

AF:

0.00188

AC:

AN:

28764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

140

186

233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00230

AC:

349

AN:

151676

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

206

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41364

American (AMR)

AF:

0.0218

AC:

333

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5090

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67808

Other (OTH)

AF:

0.00427

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00339

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Legius syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.2

Mutation Taster

=293/7

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over