chr17-31232043-ATTTTTT-A

Position:

• chr17-31232043-ATTTTTT-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6 BS2_Supporting

The NM_001042492.3(NF1):​c.3198-9_3198-4delTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 589,836 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: NF1 NM_001042492.3 splice_region, intron
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.14

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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 17-31232043-ATTTTTT-A is Benign according to our data. Variant chr17-31232043-ATTTTTT-A is described in ClinVar as [Likely_benign]. Clinvar id is 3354366.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 12 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NF1	NM_001042492.3	c.3198-9_3198-4delTTTTTT		splice_region_variant, intron_variant		ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.3198-9_3198-4delTTTTTT		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.3198-9_3198-4delTTTTTT		splice_region_variant, intron_variant		1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.000132 AC: 12 AN: 90908 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00127

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000835

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000158 AC: 79 AN: 498928 Hom.: 1 AF XY: 0.000156 AC XY: 41 AN XY: 262380

Gnomad4 AFR exome AF: 0.00207

Gnomad4 AMR exome AF: 0.000125

Gnomad4 ASJ exome AF: 0.0000818

Gnomad4 EAS exome AF: 0.000179

Gnomad4 SAS exome AF: 0.0000699

Gnomad4 FIN exome AF: 0.0000693

Gnomad4 NFE exome AF: 0.000115

Gnomad4 OTH exome AF: 0.000321

GnomAD4 genome AF: 0.000132 AC: 12 AN: 90908 Hom.: 0 Cov.: 0 AF XY: 0.000214 AC XY: 9 AN XY: 42040

Gnomad4 AFR AF: 0.000178

Gnomad4 AMR AF: 0.000135

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00127

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000835

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

NF1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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;