rs7182445

Variant names:

• chr15-38322324-G-A
• rs7182445
• NM_152594.3:c.291G>A
• SPRED1 p.Lys97Lys

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_152594.3(SPRED1):​c.291G>A​(p.Lys97Lys) variant causes a synonymous change. The variant allele was found at a frequency of 0.882 in 1,613,722 control chromosomes in the GnomAD database, including 630,054 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: 31)
  • Exomes 𝑓: 0.89 (577616 hom.)
• Consequence: SPRED1 NM_152594.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:16 O:1
• Conservation: PhyloP100: 3.71
• Publications: 22 publications found

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

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 15-38322324-G-A is Benign according to our data. Variant chr15-38322324-G-A is described in ClinVar as Benign. ClinVar VariationId is 41371.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.

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.291G>A	p.Lys97Lys	synonymous	Exon 3 of 7	NP_689807.1	Q7Z699

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRED1	ENST00000299084.9	TSL:1 MANE Select	c.291G>A	p.Lys97Lys	synonymous	Exon 3 of 7	ENSP00000299084.4	Q7Z699
	SPRED1	ENST00000881380.1		c.327G>A	p.Lys109Lys	synonymous	Exon 4 of 8	ENSP00000551439.1
	SPRED1	ENST00000951939.1		c.312G>A	p.Lys104Lys	synonymous	Exon 4 of 8	ENSP00000621998.1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125286 AN: 151994 Hom.: 52426 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.829

GnomAD2 exomes AF: 0.865 AC: 217376 AN: 251190 AF XY: 0.873

Gnomad AFR exome AF: 0.654

Gnomad AMR exome AF: 0.826

Gnomad ASJ exome AF: 0.908

Gnomad EAS exome AF: 0.790

Gnomad FIN exome AF: 0.934

Gnomad NFE exome AF: 0.896

Gnomad OTH exome AF: 0.871

GnomAD4 exome AF: 0.888 AC: 1297603 AN: 1461610 Hom.: 577616 Cov.: 53 AF XY: 0.889 AC XY: 646274 AN XY: 727112

African (AFR) AF: 0.646 AC: 21625 AN: 33466

American (AMR) AF: 0.832 AC: 37200 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 23683 AN: 26122

East Asian (EAS) AF: 0.784 AC: 31094 AN: 39636

South Asian (SAS) AF: 0.892 AC: 76943 AN: 86254

European-Finnish (FIN) AF: 0.933 AC: 49820 AN: 53412

Middle Eastern (MID) AF: 0.840 AC: 4841 AN: 5762

European-Non Finnish (NFE) AF: 0.899 AC: 999563 AN: 1111858

Other (OTH) AF: 0.875 AC: 52834 AN: 60386

GnomAD4 genome AF: 0.824 AC: 125349 AN: 152112 Hom.: 52438 Cov.: 31 AF XY: 0.826 AC XY: 61407 AN XY: 74352

African (AFR) AF: 0.664 AC: 27514 AN: 41444

American (AMR) AF: 0.841 AC: 12863 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 3127 AN: 3468

East Asian (EAS) AF: 0.792 AC: 4089 AN: 5164

South Asian (SAS) AF: 0.878 AC: 4234 AN: 4824

European-Finnish (FIN) AF: 0.933 AC: 9888 AN: 10594

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.896 AC: 60970 AN: 68010

Other (OTH) AF: 0.822 AC: 1740 AN: 2116

Alfa AF: 0.864 Hom.: 158428

Bravo AF: 0.806

Asia WGS AF: 0.795 AC: 2766 AN: 3476

EpiCase AF: 0.889

EpiControl AF: 0.886

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	Legius syndrome (7)
-	-	6	not specified (6)
-	-	3	not provided (3)
-	-	1	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	10
DANN	Benign	0.66
PhyloP100		3.7
Mutation Taster		=98/2	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7182445;

hg19: chr15-38614525;

COSMIC: COSV54434943;