rs1123232

Positions:

• chr17-31096971-A-G
• chr17-31096971-A-T

Variant summary

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

The NM_001042492.3(NF1):​c.60+1602A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,130 control chromosomes in the GnomAD database, including 25,966 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 0.54 (25966 hom., cov: 32)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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=-0.91).
• 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.60+1602A>G		intron_variant		ENST00000358273.9
NF1	NM_000267.3	c.60+1602A>G		intron_variant
NF1	NM_001128147.3	c.60+1602A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9	c.60+1602A>G		intron_variant		1	NM_001042492.3	P1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82213 AN: 152012 Hom.: 25966 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.541 AC: 82235 AN: 152130 Hom.: 25966 Cov.: 32 AF XY: 0.539 AC XY: 40044 AN XY: 74350

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.769

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.611

Alfa AF: 0.684 Hom.: 34381

Bravo AF: 0.521

Asia WGS AF: 0.571 AC: 1983 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.53

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: rs1123232; hg19: chr17-29423989;