Genetic Variant SPRED1:c.-152C>T (chr15-38253034-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_152594.3(SPRED1):c.-152C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000805 in 708,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

SPRED1
NM_152594.3 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.05

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

SPRED1 links:

ENSG00000310144 (HGNC:):

ENSG00000310144 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000659 (10/151698) while in subpopulation AMR AF = 0.000655 (10/15264). AF 95% confidence interval is 0.000355. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRED1	NM_152594.3 link	c.-152C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	ENST00000299084.9	NP_689807.1	Q7Z699
SPRED1	NM_152594.3 link	c.-152C>T		5_prime_UTR_variant	Exon 1 of 7	ENST00000299084.9	NP_689807.1	Q7Z699

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPRED1	ENST00000299084.9 link	c.-152C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 7	1	NM_152594.3	ENSP00000299084.4		Q7Z699
SPRED1	ENST00000299084.9 link	c.-152C>T		5_prime_UTR_variant	Exon 1 of 7	1	NM_152594.3	ENSP00000299084.4		Q7Z699

Frequencies

GnomAD3 genomes

AF:

0.0000659

AC:

AN:

151698

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000844

AC:

AN:

556774

Hom.:

Cov.:

AF XY:

0.0000536

AC XY:

AN XY:

298314

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15574

American (AMR)

AF:

0.00136

AC:

AN:

33092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18852

East Asian (EAS)

AF:

0.0000315

AC:

AN:

31744

South Asian (SAS)

AF:

0.00

AC:

AN:

60788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33958

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2408

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

330162

Other (OTH)

AF:

0.0000331

AC:

AN:

30196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000659

AC:

AN:

151698

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74038

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41292

American (AMR)

AF:

0.000655

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5074

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67882

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.560

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

2.0

PromoterAI

-0.0052

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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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15-38253034-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over