rs17885830

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001042492.3(NF1):c.1846-39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,608,110 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0095 ( 24 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 24 hom. )

Consequence

NF1
NM_001042492.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0610

Publications

1 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

neurofibromatosis type 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
neurofibromatosis-Noonan syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
Moyamoya disease
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
hereditary pheochromocytoma-paraganglioma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial ovarian cancer
Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

NF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 17-31225056-C-T is Benign according to our data. Variant chr17-31225056-C-T is described in ClinVar as Benign. ClinVar VariationId is 257279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00949 (1445/152204) while in subpopulation AFR AF = 0.0328 (1361/41530). AF 95% confidence interval is 0.0313. There are 24 homozygotes in GnomAd4. There are 692 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1445 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042492.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NF1	NM_001042492.3	MANE Select	c.1846-39C>T		intron	N/A	NP_001035957.1	P21359-1
	NF1	NM_000267.4		c.1846-39C>T		intron	N/A	NP_000258.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NF1	ENST00000358273.9	TSL:1 MANE Select	c.1846-39C>T	intron	N/A	ENSP00000351015.4	P21359-1
NF1	ENST00000356175.7	TSL:1	c.1846-39C>T	intron	N/A	ENSP00000348498.3	P21359-2
NF1	ENST00000579081.6	TSL:1	n.1846-39C>T	intron	N/A	ENSP00000462408.2	J3KSB5

Frequencies

GnomAD3 genomes

AF:

0.00947

AC:

1441

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00910

GnomAD2 exomes

AF:

0.00227

AC:

563

AN:

248348

AF XY:

0.00160

show subpopulations

Gnomad AFR exome

AF:

0.0309

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00103

AC:

1502

AN:

1455906

Hom.:

Cov.:

AF XY:

0.000868

AC XY:

629

AN XY:

724644

show subpopulations

African (AFR)

AF:

0.0325

AC:

1083

AN:

33354

American (AMR)

AF:

0.00201

AC:

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39626

South Asian (SAS)

AF:

0.000105

AC:

AN:

86078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51706

Middle Eastern (MID)

AF:

0.00403

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

0.000129

AC:

143

AN:

1108488

Other (OTH)

AF:

0.00256

AC:

154

AN:

60214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

155

233

310

388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00949

AC:

1445

AN:

152204

Hom.:

Cov.:

AF XY:

0.00930

AC XY:

692

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0328

AC:

1361

AN:

41530

American (AMR)

AF:

0.00360

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68000

Other (OTH)

AF:

0.00900

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

139

209

278

348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00389

Hom.:

Bravo

AF:

0.0102

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

8.9

(source)

DANN

Benign

0.66

PhyloP100

0.061

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over