rs2040792

Variant names:

• chr17-31301531-C-A
• rs2040792
• NM_001042492.3:c.4836-24289C>A

Variant summary

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

The NM_001042492.3(NF1):​c.4836-24289C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,874 control chromosomes in the GnomAD database, including 20,169 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 0.49 (20169 hom., cov: 31)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3	c.4836-24289C>A		intron_variant	Intron 36 of 57	ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.4773-24289C>A		intron_variant	Intron 35 of 56		NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.4836-24289C>A		intron_variant	Intron 36 of 57	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73950 AN: 151754 Hom.: 20164 Cov.: 31

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.487 AC: 73977 AN: 151874 Hom.: 20169 Cov.: 31 AF XY: 0.485 AC XY: 35998 AN XY: 74202

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.517

Alfa AF: 0.520 Hom.: 4239

Bravo AF: 0.463

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	-0.61
CADD	Benign	1.8
DANN	Benign	0.69

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: rs2040792; hg19: chr17-29628549;