rs3751526

Variant names:

• chr15-38351373-T-C
• rs3751526
• NM_152594.3:c.1044T>C

Your query was ambiguous. Multiple possible variants found:

• chr15-38351373-T-C
• chr15-38351373-T-A
• chr15-38351373-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_152594.3(SPRED1):​c.1044T>C​(p.Val348Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 1,613,954 control chromosomes in the GnomAD database, including 630,003 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (52379 hom., cov: 31)
  • Exomes 𝑓: 0.89 (577624 hom.)
• Consequence: SPRED1 NM_152594.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:17 O:1
• Conservation: PhyloP100: 1.23
• Publications: 23 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: ClinGen, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 15-38351373-T-C is Benign according to our data. Variant chr15-38351373-T-C is described in ClinVar as Benign. ClinVar VariationId is 41370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.23 with no splicing effect.
• 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.1044T>C	p.Val348Val	synonymous	Exon 7 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.1044T>C	p.Val348Val	synonymous	Exon 7 of 7	ENSP00000299084.4	Q7Z699
	SPRED1	ENST00000881380.1		c.1080T>C	p.Val360Val	synonymous	Exon 8 of 8	ENSP00000551439.1
	SPRED1	ENST00000951939.1		c.1065T>C	p.Val355Val	synonymous	Exon 8 of 8	ENSP00000621998.1

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125195 AN: 151996 Hom.: 52366 Cov.: 31

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.831

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.829

GnomAD2 exomes AF: 0.865 AC: 217398 AN: 251258 AF XY: 0.873

Gnomad AFR exome AF: 0.652

Gnomad AMR exome AF: 0.826

Gnomad ASJ exome AF: 0.908

Gnomad EAS exome AF: 0.789

Gnomad FIN exome AF: 0.934

Gnomad NFE exome AF: 0.896

Gnomad OTH exome AF: 0.871

GnomAD4 exome AF: 0.888 AC: 1297707 AN: 1461840 Hom.: 577624 Cov.: 72 AF XY: 0.889 AC XY: 646314 AN XY: 727228

African (AFR) AF: 0.645 AC: 21594 AN: 33474

American (AMR) AF: 0.832 AC: 37207 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 23694 AN: 26132

East Asian (EAS) AF: 0.784 AC: 31110 AN: 39698

South Asian (SAS) AF: 0.892 AC: 76946 AN: 86258

European-Finnish (FIN) AF: 0.933 AC: 49825 AN: 53418

Middle Eastern (MID) AF: 0.841 AC: 4849 AN: 5768

European-Non Finnish (NFE) AF: 0.899 AC: 999655 AN: 1111982

Other (OTH) AF: 0.875 AC: 52827 AN: 60396

GnomAD4 genome AF: 0.823 AC: 125259 AN: 152114 Hom.: 52379 Cov.: 31 AF XY: 0.825 AC XY: 61366 AN XY: 74352

African (AFR) AF: 0.662 AC: 27425 AN: 41448

American (AMR) AF: 0.842 AC: 12852 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3126 AN: 3468

East Asian (EAS) AF: 0.792 AC: 4101 AN: 5180

South Asian (SAS) AF: 0.877 AC: 4218 AN: 4808

European-Finnish (FIN) AF: 0.934 AC: 9903 AN: 10606

Middle Eastern (MID) AF: 0.829 AC: 242 AN: 292

European-Non Finnish (NFE) AF: 0.896 AC: 60978 AN: 68020

Other (OTH) AF: 0.822 AC: 1734 AN: 2110

Alfa AF: 0.871 Hom.: 125879

Bravo AF: 0.805

Asia WGS AF: 0.795 AC: 2767 AN: 3478

EpiCase AF: 0.890

EpiControl AF: 0.886

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	not specified (8)
-	-	6	Legius syndrome (7)
-	-	2	not provided (2)
-	-	1	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.7
DANN	Benign	0.77
PhyloP100		1.2
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs3751526; hg19: chr15-38643574; COSMIC: COSV54434386;