chr17-31298620-G-A

Position:

• chr17-31298620-G-A

Variant summary

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

The NM_001042492.3(NF1):​c.4836-27200G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,792 control chromosomes in the GnomAD database, including 18,575 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 0.45 (18575 hom., cov: 32)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NF1	NM_001042492.3	c.4836-27200G>A		intron_variant		ENST00000358273.9
NF1	NM_000267.3	c.4773-27200G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9	c.4836-27200G>A		intron_variant		1	NM_001042492.3	P1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68382 AN: 151674 Hom.: 18542 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.451 AC: 68475 AN: 151792 Hom.: 18575 Cov.: 32 AF XY: 0.454 AC XY: 33695 AN XY: 74164

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.385

Alfa AF: 0.398 Hom.: 2323

Bravo AF: 0.471

Asia WGS AF: 0.433 AC: 1505 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	13
DANN	Benign	0.64

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: rs9902893; hg19: chr17-29625638;