rs7215555

Positions:

• chr17-31237585-G-A
• chr17-31237585-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042492.3(NF1):​c.3974+1564G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 151,400 control chromosomes in the GnomAD database, including 44,960 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44960 hom., cov: 29)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.617

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NF1	NM_001042492.3	c.3974+1564G>A		intron_variant		ENST00000358273.9
NF1	NM_000267.3	c.3974+1564G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9	c.3974+1564G>A		intron_variant		1	NM_001042492.3	P1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115351 AN: 151284 Hom.: 44883 Cov.: 29

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.763

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.763 AC: 115495 AN: 151400 Hom.: 44960 Cov.: 29 AF XY: 0.762 AC XY: 56296 AN XY: 73916

Gnomad4 AFR AF: 0.934

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.687

Gnomad4 OTH AF: 0.765

Alfa AF: 0.698 Hom.: 18151

Bravo AF: 0.774

Asia WGS AF: 0.644 AC: 2244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.15

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: rs7215555; hg19: chr17-29564603;