rs17879551

chr17-31360442-A-Cchr17-31360442-A-Gchr17-31360442-A-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001042492.3(NF1):c.8161-45A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000877 in 1,546,772 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (1 hom.)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.757

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-31360442-A-C is Benign according to our data. Variant chr17-31360442-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 257307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 265 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NF1	NM_001042492.3	c.8161-45A>C		intron_variant		ENST00000358273.9
NF1	NM_000267.3	c.8098-45A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NF1	ENST00000358273.9	c.8161-45A>C		intron_variant		1	NM_001042492.3	P1

Frequencies

GnomAD3 genomes AF: 0.00174 AC: 265 AN: 152206 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.00573

GnomAD3 exomes AF: 0.00108 AC: 269 AN: 248016 Hom.: 0 AF XY: 0.00112 AC XY: 151 AN XY: 134678

Gnomad AFR exome AF: 0.00244

Gnomad AMR exome AF: 0.00163

Gnomad ASJ exome AF: 0.00418

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000951

Gnomad OTH exome AF: 0.00365

GnomAD4 exome AF: 0.000782 AC: 1091 AN: 1394448 Hom.: 1 Cov.: 23 AF XY: 0.000793 AC XY: 553 AN XY: 697678

Gnomad4 AFR exome AF: 0.00199

Gnomad4 AMR exome AF: 0.00179

Gnomad4 ASJ exome AF: 0.00458

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.000165

Gnomad4 FIN exome AF: 0.0000578

Gnomad4 NFE exome AF: 0.000632

Gnomad4 OTH exome AF: 0.00192

GnomAD4 genome AF: 0.00174 AC: 265 AN: 152324 Hom.: 2 Cov.: 32 AF XY: 0.00184 AC XY: 137 AN XY: 74486

Gnomad4 AFR AF: 0.00243

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00231 Hom.: 0

Bravo AF: 0.00226

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Neurofibromatosis, familial spinal Benign:1

Likely benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	13
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs17879551; hg19: chr17-29687460; COSMIC: COSV104420395;