rs2272105

Variant names:

• chr15-38299584-A-G
• rs2272105
• NM_152594.3:c.207+37A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-38299584-A-G
• chr15-38299584-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152594.3(SPRED1):​c.207+37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,582,056 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (57 hom.)
• Consequence: SPRED1 NM_152594.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.394
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 15-38299584-A-G is Benign according to our data. Variant chr15-38299584-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0509 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.207+37A>G		intron	N/A	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.207+37A>G		intron	N/A	ENSP00000299084.4	Q7Z699
	SPRED1	ENST00000881380.1		c.243+37A>G		intron	N/A	ENSP00000551439.1
	SPRED1	ENST00000951939.1		c.207+37A>G		intron	N/A	ENSP00000621998.1

Frequencies

GnomAD3 genomes AF: 0.00195 AC: 297 AN: 152212 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0524

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00497 AC: 1171 AN: 235608 AF XY: 0.00485

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0663

Gnomad FIN exome AF: 0.0000962

Gnomad NFE exome AF: 0.000297

Gnomad OTH exome AF: 0.000680

GnomAD4 exome AF: 0.00165 AC: 2363 AN: 1429726 Hom.: 57 Cov.: 26 AF XY: 0.00161 AC XY: 1145 AN XY: 712852

African (AFR) AF: 0.00 AC: 0 AN: 32082

American (AMR) AF: 0.0000451 AC: 2 AN: 44356

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25946

East Asian (EAS) AF: 0.0528 AC: 2024 AN: 38328

South Asian (SAS) AF: 0.000802 AC: 68 AN: 84750

European-Finnish (FIN) AF: 0.000190 AC: 10 AN: 52750

Middle Eastern (MID) AF: 0.000884 AC: 5 AN: 5656

European-Non Finnish (NFE) AF: 0.000126 AC: 137 AN: 1086798

Other (OTH) AF: 0.00198 AC: 117 AN: 59060

GnomAD4 genome AF: 0.00194 AC: 296 AN: 152330 Hom.: 9 Cov.: 32 AF XY: 0.00207 AC XY: 154 AN XY: 74482

African (AFR) AF: 0.00 AC: 0 AN: 41578

American (AMR) AF: 0.000327 AC: 5 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0525 AC: 272 AN: 5182

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4826

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68036

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000370 Hom.: 1

Bravo AF: 0.00287

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Legius syndrome (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.41
PhyloP100		0.39
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

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

Other links and lift over

dbSNP: rs2272105;

hg19: chr15-38591785;

COSMIC: COSV54438959;