17-31336607-TAA-TAAAAA

Variant summary

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

The NM_001042492.3(NF1):c.6148-19_6148-17dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,415,564 control chromosomes in the GnomAD database, including 38 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (14 hom., cov: 0)
  • Exomes 𝑓: 0.012 (24 hom.)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.877

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 -10 ACMG points.

• BP6: Variant 17-31336607-T-TAAA is Benign according to our data. Variant chr17-31336607-T-TAAA is described in ClinVar as [Likely_benign]. Clinvar id is 1186284.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00764 (1143/149616) while in subpopulation SAS AF= 0.0109 (52/4752). AF 95% confidence interval is 0.01. There are 14 homozygotes in gnomad4. There are 579 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd at 1135 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NF1	NM_001042492.3	c.6148-19_6148-17dup		intron_variant		ENST00000358273.9
NF1	NM_000267.3	c.6085-19_6085-17dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9	c.6148-19_6148-17dup		intron_variant		1	NM_001042492.3	P1

Frequencies

GnomAD3 genomes AF: 0.00759 AC: 1135 AN: 149530 Hom.: 12 Cov.: 0

Gnomad AFR AF: 0.00175

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00520

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00195

Gnomad SAS AF: 0.0111

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.00649

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.00876

GnomAD3 exomes AF: 0.0132 AC: 1842 AN: 139834 Hom.: 18 AF XY: 0.0134 AC XY: 1014 AN XY: 75790

Gnomad AFR exome AF: 0.00254

Gnomad AMR exome AF: 0.00792

Gnomad ASJ exome AF: 0.0220

Gnomad EAS exome AF: 0.00290

Gnomad SAS exome AF: 0.0123

Gnomad FIN exome AF: 0.0211

Gnomad NFE exome AF: 0.0153

Gnomad OTH exome AF: 0.0156

GnomAD4 exome AF: 0.0118 AC: 14896 AN: 1265948 Hom.: 24 Cov.: 33 AF XY: 0.0121 AC XY: 7562 AN XY: 627486

Gnomad4 AFR exome AF: 0.00274

Gnomad4 AMR exome AF: 0.00757

Gnomad4 ASJ exome AF: 0.0208

Gnomad4 EAS exome AF: 0.00623

Gnomad4 SAS exome AF: 0.0131

Gnomad4 FIN exome AF: 0.0182

Gnomad4 NFE exome AF: 0.0117

Gnomad4 OTH exome AF: 0.0119

GnomAD4 genome AF: 0.00764 AC: 1143 AN: 149616 Hom.: 14 Cov.: 0 AF XY: 0.00794 AC XY: 579 AN XY: 72956

Gnomad4 AFR AF: 0.00202

Gnomad4 AMR AF: 0.00519

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00195

Gnomad4 SAS AF: 0.0109

Gnomad4 FIN AF: 0.0135

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.00868

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

Aug 18, 2019

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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: rs33925668; hg19: chr17-29663625;