rs1123232

Variant names:

• chr17-31096971-A-G
• rs1123232
• NM_001042492.3:c.60+1602A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-31096971-A-G
• chr17-31096971-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042492.3(NF1):​c.60+1602A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,130 control chromosomes in the GnomAD database, including 25,966 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (25966 hom., cov: 32)
• Consequence: NF1 NM_001042492.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 10 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NF1	NM_001042492.3	c.60+1602A>G		intron_variant	Intron 1 of 57	ENST00000358273.9	NP_001035957.1
NF1	NM_000267.4	c.60+1602A>G		intron_variant	Intron 1 of 56		NP_000258.1
NF1	NM_001128147.3	c.60+1602A>G		intron_variant	Intron 1 of 14		NP_001121619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NF1	ENST00000358273.9	c.60+1602A>G		intron_variant	Intron 1 of 57	1	NM_001042492.3	ENSP00000351015.4

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82213 AN: 152012 Hom.: 25966 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.610

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.541 AC: 82235 AN: 152130 Hom.: 25966 Cov.: 32 AF XY: 0.539 AC XY: 40044 AN XY: 74350

African (AFR) AF: 0.196 AC: 8122 AN: 41518

American (AMR) AF: 0.555 AC: 8476 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 2667 AN: 3470

East Asian (EAS) AF: 0.563 AC: 2921 AN: 5184

South Asian (SAS) AF: 0.625 AC: 3017 AN: 4826

European-Finnish (FIN) AF: 0.659 AC: 6952 AN: 10544

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.705 AC: 47910 AN: 67996

Other (OTH) AF: 0.611 AC: 1292 AN: 2114

Alfa AF: 0.660 Hom.: 42233

Bravo AF: 0.521

Asia WGS AF: 0.571 AC: 1983 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.53
PhyloP100		-2.0
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1123232; hg19: chr17-29423989;