rs17881173

Positions:

• chr17-31200391-ATTATC-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The ENST00000358273.9(NF1):​c.889-25_889-21del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000242 in 1,609,282 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (1 hom.)
• Consequence: NF1 ENST00000358273.9 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.502

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.

• BP6: Variant 17-31200391-ATTATC-A is Benign according to our data. Variant chr17-31200391-ATTATC-A is described in ClinVar as [Benign]. Clinvar id is 257309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-31200391-ATTATC-A is described in Lovd as [Benign].
• BS2: High AC in GnomAd4 at 172 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NF1	NM_001042492.3	c.889-25_889-21del		intron_variant		ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.889-25_889-21del		intron_variant			NP_000258.1
NF1	NM_001128147.3	c.889-25_889-21del		intron_variant			NP_001121619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.889-25_889-21del		intron_variant		1	NM_001042492.3	ENSP00000351015	P1

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 171 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00381

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000321 AC: 80 AN: 249578 Hom.: 0 AF XY: 0.000244 AC XY: 33 AN XY: 135144

Gnomad AFR exome AF: 0.00364

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000149 AC: 217 AN: 1456944 Hom.: 1 AF XY: 0.000117 AC XY: 85 AN XY: 725154

Gnomad4 AFR exome AF: 0.00407

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000388

Gnomad4 OTH exome AF: 0.000448

GnomAD4 genome AF: 0.00113 AC: 172 AN: 152338 Hom.: 0 Cov.: 32 AF XY: 0.00102 AC XY: 76 AN XY: 74496

Gnomad4 AFR AF: 0.00382

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000868 Hom.: 0

Bravo AF: 0.00126

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Dec 07, 2016	- -

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: rs17881173; hg19: chr17-29527409;