rs3815156

Positions:

• chr17-31358132-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001042492.3(NF1):​c.7971-348A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 353,120 control chromosomes in the GnomAD database, including 8,425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (3049 hom., cov: 32)
  • Exomes 𝑓: 0.21 (5376 hom.)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.82

Genes affected

NF1 (HGNC:7765): (neurofibromin 1) This gene product appears to function as a negative regulator of the ras signal transduction pathway. Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The mRNA for this gene is subject to RNA editing (CGA>UGA->Arg1306Term) resulting in premature translation termination. Alternatively spliced transcript variants encoding different isoforms have also been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-31358132-A-G is Benign according to our data. Variant chr17-31358132-A-G is described in ClinVar as [Benign]. Clinvar id is 561764.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NF1	NM_001042492.3	c.7971-348A>G		intron_variant		ENST00000358273.9
NF1	NM_000267.3	c.7908-348A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9	c.7971-348A>G		intron_variant		1	NM_001042492.3	P1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26579 AN: 152028 Hom.: 3040 Cov.: 32

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.165

GnomAD4 exome AF: 0.213 AC: 42899 AN: 200972 Hom.: 5376 Cov.: 0 AF XY: 0.222 AC XY: 24201 AN XY: 109098

Gnomad4 AFR exome AF: 0.0541

Gnomad4 AMR exome AF: 0.321

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.437

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.175 AC: 26607 AN: 152148 Hom.: 3049 Cov.: 32 AF XY: 0.184 AC XY: 13651 AN XY: 74366

Gnomad4 AFR AF: 0.0583

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.167

Alfa AF: 0.167 Hom.: 359

Bravo AF: 0.172

Asia WGS AF: 0.359 AC: 1244 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.41

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

Other links and lift over

dbSNP: rs3815156; hg19: chr17-29685150;