17-31232043-ATTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTTT

Position:

• chr17-31232043-ATTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001042492.3(NF1):​c.3198-6_3198-4dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0073 (82 hom., cov: 0)
  • Exomes 𝑓: 0.013 (61 hom.)
• Consequence: NF1 NM_001042492.3 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.50

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]

NF1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-31232043-A-ATTT is Benign according to our data. Variant chr17-31232043-A-ATTT is described in ClinVar as [Likely_benign]. Clinvar id is 1220234.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00725 (659/90896) while in subpopulation AFR AF= 0.0279 (627/22454). AF 95% confidence interval is 0.0261. There are 82 homozygotes in gnomad4. There are 314 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 659 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NF1	NM_001042492.3	c.3198-6_3198-4dupTTT		splice_region_variant, intron_variant		ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.3198-6_3198-4dupTTT		splice_region_variant, intron_variant			NP_000258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.3198-6_3198-4dupTTT		splice_region_variant, intron_variant		1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.00724 AC: 658 AN: 90900 Hom.: 82 Cov.: 0

Gnomad AFR AF: 0.0279

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000943

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00220

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000334

Gnomad OTH AF: 0.00246

GnomAD3 exomes AF: 0.0196 AC: 1275 AN: 65012 Hom.: 24 AF XY: 0.0182 AC XY: 637 AN XY: 34954

Gnomad AFR exome AF: 0.0489

Gnomad AMR exome AF: 0.0366

Gnomad ASJ exome AF: 0.0134

Gnomad EAS exome AF: 0.0494

Gnomad SAS exome AF: 0.0170

Gnomad FIN exome AF: 0.00194

Gnomad NFE exome AF: 0.0135

Gnomad OTH exome AF: 0.0239

GnomAD4 exome AF: 0.0129 AC: 6426 AN: 497916 Hom.: 61 Cov.: 4 AF XY: 0.0135 AC XY: 3545 AN XY: 261784

Gnomad4 AFR exome AF: 0.0220

Gnomad4 AMR exome AF: 0.0259

Gnomad4 ASJ exome AF: 0.0101

Gnomad4 EAS exome AF: 0.0210

Gnomad4 SAS exome AF: 0.0293

Gnomad4 FIN exome AF: 0.00966

Gnomad4 NFE exome AF: 0.00994

Gnomad4 OTH exome AF: 0.0142

GnomAD4 genome AF: 0.00725 AC: 659 AN: 90896 Hom.: 82 Cov.: 0 AF XY: 0.00747 AC XY: 314 AN XY: 42042

Gnomad4 AFR AF: 0.0279

Gnomad4 AMR AF: 0.000942

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00221

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000334

Gnomad4 OTH AF: 0.00245

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs371047262; hg19: chr17-29559061;