17-31219157-T-C

Variant names:

• chr17-31219157-T-C
• rs2905880
• ENST00000487476.5:c.*24T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000487476.5(NF1):​c.*24T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 1,586,932 control chromosomes in the GnomAD database, including 355,906 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (25753 hom., cov: 30)
  • Exomes 𝑓: 0.67 (330153 hom.)
• Consequence: NF1 ENST00000487476.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.554

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-31219157-T-C is Benign according to our data. Variant chr17-31219157-T-C is described in ClinVar as [Benign]. Clinvar id is 257278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3	c.1641+39T>C		intron_variant	Intron 14 of 57	ENST00000358273.9	NP_001035957.1
NF1	NM_000267.3	c.1641+39T>C		intron_variant	Intron 14 of 56		NP_000258.1
NF1	NM_001128147.3	c.1641+39T>C		intron_variant	Intron 14 of 14		NP_001121619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.1641+39T>C		intron_variant	Intron 14 of 57	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81544 AN: 151730 Hom.: 25762 Cov.: 30

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.605

GnomAD3 exomes AF: 0.621 AC: 138781 AN: 223626 Hom.: 44945 AF XY: 0.637 AC XY: 76392 AN XY: 119906

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.506

Gnomad ASJ exome AF: 0.777

Gnomad EAS exome AF: 0.564

Gnomad SAS exome AF: 0.631

Gnomad FIN exome AF: 0.664

Gnomad NFE exome AF: 0.700

Gnomad OTH exome AF: 0.670

GnomAD4 exome AF: 0.672 AC: 963725 AN: 1435084 Hom.: 330153 Cov.: 26 AF XY: 0.673 AC XY: 479547 AN XY: 712478

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.512

Gnomad4 ASJ exome AF: 0.775

Gnomad4 EAS exome AF: 0.556

Gnomad4 SAS exome AF: 0.634

Gnomad4 FIN exome AF: 0.657

Gnomad4 NFE exome AF: 0.698

Gnomad4 OTH exome AF: 0.660

GnomAD4 genome AF: 0.537 AC: 81528 AN: 151848 Hom.: 25753 Cov.: 30 AF XY: 0.534 AC XY: 39625 AN XY: 74174

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.606

Alfa AF: 0.619 Hom.: 8213

Bravo AF: 0.517

Asia WGS AF: 0.567 AC: 1972 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 06, 2018

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Neurofibromatosis, type 1 Benign:2

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Jun 20, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Neurofibromatosis, familial spinal Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.9
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2905880; hg19: chr17-29546175; COSMIC: COSV62217232;