dbSNP rs755489788: SPRED1:c.-18G>C (chr15-38253168-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152594.3(SPRED1):c.-18G>C variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00000254 in 1,575,712 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 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SPRED1
NM_152594.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.12

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SPRED1	NM_152594.3 link	c.-18G>C	5_prime_UTR_variant	Exon 1 of 7	ENST00000299084.9	NP_689807.1	Q7Z699
SPRED1	XM_005254202.4 link	c.-18G>C	5_prime_UTR_variant	Exon 1 of 8		XP_005254259.1
SPRED1	XM_047432199.1 link	c.-181G>C	5_prime_UTR_variant	Exon 1 of 9		XP_047288155.1
SPRED1	XM_047432200.1 link	c.-145G>C	5_prime_UTR_variant	Exon 1 of 8		XP_047288156.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPRED1	ENST00000299084.9 link	c.-18G>C	5_prime_UTR_variant	Exon 1 of 7	1	NM_152594.3	ENSP00000299084.4	Q7Z699
SPRED1	ENST00000561205.1 link	n.321G>C	non_coding_transcript_exon_variant	Exon 1 of 5	5
ENSG00000310144	ENST00000847565.1 link	n.95+399C>G	intron_variant	Intron 1 of 1
SPRED1	ENST00000561317.1 link	c.-145G>C	upstream_gene_variant		4		ENSP00000453680.1	H0YMN8

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1423598

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

704406

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32620

American (AMR)

AF:

0.00

AC:

AN:

39738

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25488

East Asian (EAS)

AF:

0.00

AC:

AN:

37726

South Asian (SAS)

AF:

0.00

AC:

AN:

81182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091770

Other (OTH)

AF:

0.0000170

AC:

AN:

58990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41414

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000108

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

5.1

PromoterAI

-0.041

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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rs755489788

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