rs7179118

Variant names:

• chr15-38339719-G-A
• rs7179118
• NM_152594.3:c.424-18G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-38339719-G-A
• chr15-38339719-G-T

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.424-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,610,272 control chromosomes in the GnomAD database, including 49,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.23 (4372 hom., cov: 32)
  • Exomes 𝑓: 0.24 (45346 hom.)
• Consequence: SPRED1 NM_152594.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.0500
• Publications: 5 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, Ambry Genetics, Genomics England PanelApp, ClinGen, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 15-38339719-G-A is Benign according to our data. Variant chr15-38339719-G-A is described in ClinVar as Benign. ClinVar VariationId is 41452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 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.424-18G>A		intron	N/A	NP_689807.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRED1	ENST00000299084.9	TSL:1 MANE Select	c.424-18G>A		intron	N/A	ENSP00000299084.4
	SPRED1	ENST00000881380.1		c.460-18G>A		intron	N/A	ENSP00000551439.1
	SPRED1	ENST00000951939.1		c.445-18G>A		intron	N/A	ENSP00000621998.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35643 AN: 151874 Hom.: 4372 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0326

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.244

GnomAD2 exomes AF: 0.223 AC: 56008 AN: 250910 AF XY: 0.226

Gnomad AFR exome AF: 0.221

Gnomad AMR exome AF: 0.179

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.0313

Gnomad FIN exome AF: 0.285

Gnomad NFE exome AF: 0.265

Gnomad OTH exome AF: 0.256

GnomAD4 exome AF: 0.244 AC: 356131 AN: 1458280 Hom.: 45346 Cov.: 31 AF XY: 0.243 AC XY: 176195 AN XY: 725568

African (AFR) AF: 0.222 AC: 7423 AN: 33368

American (AMR) AF: 0.184 AC: 8215 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 6407 AN: 26094

East Asian (EAS) AF: 0.0478 AC: 1893 AN: 39628

South Asian (SAS) AF: 0.175 AC: 15064 AN: 86200

European-Finnish (FIN) AF: 0.283 AC: 15078 AN: 53278

Middle Eastern (MID) AF: 0.303 AC: 1742 AN: 5756

European-Non Finnish (NFE) AF: 0.258 AC: 286159 AN: 1108998

Other (OTH) AF: 0.235 AC: 14150 AN: 60266

GnomAD4 genome AF: 0.235 AC: 35655 AN: 151992 Hom.: 4372 Cov.: 32 AF XY: 0.231 AC XY: 17200 AN XY: 74304

African (AFR) AF: 0.229 AC: 9519 AN: 41484

American (AMR) AF: 0.193 AC: 2944 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 842 AN: 3466

East Asian (EAS) AF: 0.0327 AC: 169 AN: 5176

South Asian (SAS) AF: 0.179 AC: 860 AN: 4806

European-Finnish (FIN) AF: 0.281 AC: 2965 AN: 10552

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17646 AN: 67940

Other (OTH) AF: 0.241 AC: 509 AN: 2110

Alfa AF: 0.253 Hom.: 894

Bravo AF: 0.229

Asia WGS AF: 0.104 AC: 359 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Legius syndrome (5)
-	-	5	not specified (5)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.67
PhyloP100		-0.050
BranchPoint Hunter		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs7179118; hg19: chr15-38631920; COSMIC: COSV54438533;