rs12603885

chr17-31139704-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.61-16279G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,974 control chromosomes in the GnomAD database, including 26,703 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 0.56 (26703 hom., cov: 31)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NF1	NM_001042492.3	c.61-16279G>A		intron_variant		ENST00000358273.9
NF1	NM_000267.3	c.61-16279G>A		intron_variant
NF1	NM_001128147.3	c.61-16279G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9	c.61-16279G>A		intron_variant		1	NM_001042492.3	P1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85305 AN: 151856 Hom.: 26710 Cov.: 31

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.561 AC: 85305 AN: 151974 Hom.: 26703 Cov.: 31 AF XY: 0.558 AC XY: 41436 AN XY: 74278

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.623

Alfa AF: 0.577 Hom.: 4993

Bravo AF: 0.544

Asia WGS AF: 0.574 AC: 1998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.39
Dann	Benign	0.57

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: rs12603885; hg19: chr17-29466722;