Genetic Variant NF1:c.3198-8_3198-4dupTTTTT (chr17-31232043-A-ATTTTT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001042492.3(NF1):c.3198-8_3198-4dupTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000022 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

NF1
NM_001042492.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50

Publications

2 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: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, G2P, Genomics England PanelApp
neurofibromatosis-Noonan syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, PanelApp Australia
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: AD Classification: NO_KNOWN Submitted by: ClinGen

NF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 554 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NF1	NM_001042492.3	MANE Select	c.3198-8_3198-4dupTTTTT		splice_region intron	N/A	NP_001035957.1
	NF1	NM_000267.4		c.3198-8_3198-4dupTTTTT		splice_region intron	N/A	NP_000258.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NF1	ENST00000358273.9	TSL:1 MANE Select	c.3198-30_3198-29insTTTTT	intron	N/A	ENSP00000351015.4
NF1	ENST00000356175.7	TSL:1	c.3198-30_3198-29insTTTTT	intron	N/A	ENSP00000348498.3
NF1	ENST00000579081.6	TSL:1	n.3198-30_3198-29insTTTTT	intron	N/A	ENSP00000462408.2

Frequencies

GnomAD3 genomes

AF:

0.0000220

AC:

AN:

90908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000446

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000209

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00111

AC:

554

AN:

498906

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

295

AN XY:

262364

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

10162

American (AMR)

AF:

0.00250

AC:

AN:

16030

Ashkenazi Jewish (ASJ)

AF:

0.000982

AC:

AN:

12226

East Asian (EAS)

AF:

0.00143

AC:

AN:

16802

South Asian (SAS)

AF:

0.00247

AC:

106

AN:

42928

European-Finnish (FIN)

AF:

0.000832

AC:

AN:

28842

Middle Eastern (MID)

AF:

0.00119

AC:

AN:

1682

European-Non Finnish (NFE)

AF:

0.000870

AC:

303

AN:

348398

Other (OTH)

AF:

0.000916

AC:

AN:

21836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000220

AC:

AN:

90908

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

42040

show subpopulations

African (AFR)

AF:

0.0000446

AC:

AN:

22426

American (AMR)

AF:

0.00

AC:

AN:

7422

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2612

East Asian (EAS)

AF:

0.00

AC:

AN:

2728

South Asian (SAS)

AF:

0.00

AC:

AN:

2360

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

196

European-Non Finnish (NFE)

AF:

0.0000209

AC:

AN:

47886

Other (OTH)

AF:

0.00

AC:

AN:

1220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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17-31232043-ATTTTTTTTTTTTTTT-ATTTTTTTTTTTTTTTTTTTT

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