17-31286582-G-C

Variant names:

• chr17-31286582-G-C
• rs4795593
• NM_001042492.3:c.4835+21243G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042492.3(NF1):​c.4835+21243G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 151,968 control chromosomes in the GnomAD database, including 16,520 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 0.43 (16520 hom., cov: 32)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227
• Publications: 8 publications found

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]

OMG (HGNC:8135): (oligodendrocyte myelin glycoprotein) Predicted to enable identical protein binding activity. Predicted to be involved in neuron projection regeneration. Predicted to act upstream of or within regulation of collateral sprouting of intact axon in response to injury. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042492.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NF1	NM_001042492.3	MANE Select	c.4835+21243G>C		intron	N/A	NP_001035957.1
	NF1	NM_000267.4		c.4772+21243G>C		intron	N/A	NP_000258.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NF1	ENST00000358273.9	TSL:1 MANE Select	c.4835+21243G>C		intron	N/A	ENSP00000351015.4
	NF1	ENST00000356175.7	TSL:1	c.4772+21243G>C		intron	N/A	ENSP00000348498.3
	NF1	ENST00000579081.6	TSL:1	n.4773-12928G>C		intron	N/A	ENSP00000462408.2

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65519 AN: 151848 Hom.: 16494 Cov.: 32

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.443

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.432 AC: 65599 AN: 151968 Hom.: 16520 Cov.: 32 AF XY: 0.435 AC XY: 32331 AN XY: 74270

African (AFR) AF: 0.697 AC: 28860 AN: 41426

American (AMR) AF: 0.451 AC: 6885 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 812 AN: 3462

East Asian (EAS) AF: 0.444 AC: 2304 AN: 5184

South Asian (SAS) AF: 0.376 AC: 1813 AN: 4816

European-Finnish (FIN) AF: 0.345 AC: 3638 AN: 10548

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20180 AN: 67942

Other (OTH) AF: 0.371 AC: 784 AN: 2112

Alfa AF: 0.213 Hom.: 432

Bravo AF: 0.449

Asia WGS AF: 0.427 AC: 1484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.78
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4795593; hg19: chr17-29613600;