Variant 15-38252854-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_152594.3(SPRED1):c.-332G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 419,478 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 5 hom., cov: 31)

Exomes 𝑓: 0.00074 ( 1 hom. )

Consequence

SPRED1
NM_152594.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0970

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-38252854-G-A is Benign according to our data. Variant chr15-38252854-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1216131.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00667 (1016/152238) while in subpopulation AFR AF= 0.023 (954/41552). AF 95% confidence interval is 0.0217. There are 5 homozygotes in gnomad4. There are 464 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1016 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
SPRED1	NM_152594.3 linkuse as main transcript	c.-332G>A	5_prime_UTR_variant	1/7	ENST00000299084.9
SPRED1	XM_005254202.4 linkuse as main transcript	c.-332G>A	5_prime_UTR_variant	1/8
SPRED1	XM_047432199.1 linkuse as main transcript	c.-495G>A	5_prime_UTR_variant	1/9
SPRED1	XM_047432200.1 linkuse as main transcript	c.-459G>A	5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPRED1	ENST00000299084.9 linkuse as main transcript	c.-332G>A		5_prime_UTR_variant	1/7	1	NM_152594.3	P1
SPRED1	ENST00000561205.1 linkuse as main transcript	n.7G>A		non_coding_transcript_exon_variant	1/5	5

Frequencies

GnomAD3 genomes

AF:

0.00667

AC:

1015

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

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:

0.00431

GnomAD4 exome

AF:

0.000737

AC:

197

AN:

267240

Hom.:

Cov.:

AF XY:

0.000630

AC XY:

AN XY:

142780

show subpopulations

Gnomad4 AFR exome

AF:

0.0219

Gnomad4 AMR exome

AF:

0.00122

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000518

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000572

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.00667

AC:

1016

AN:

152238

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

464

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0230

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00576

Hom.:

Bravo

AF:

0.00803

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.89

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over