rs556823296

Variant names:

• chr17-31095288-G-C
• rs556823296
• NM_001042492.3:c.-22G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-31095288-G-C
• chr17-31095288-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001042492.3(NF1):​c.-22G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00598 in 1,534,806 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (1 hom., cov: 30)
  • Exomes 𝑓: 0.0062 (33 hom.)
• Consequence: NF1 NM_001042492.3 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 1.40
• Publications: 1 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]

MIR4733HG (HGNC:55332): (MIR4733 host gene)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 17-31095288-G-C is Benign according to our data. Variant chr17-31095288-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00384 (583/151872) while in subpopulation NFE AF = 0.00597 (405/67892). AF 95% confidence interval is 0.00549. There are 1 homozygotes in GnomAd4. There are 269 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 583 AD,Unknown 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.-22G>C		5_prime_UTR	Exon 1 of 58	NP_001035957.1	P21359-1
	NF1	NM_000267.4		c.-22G>C		5_prime_UTR	Exon 1 of 57	NP_000258.1
	NF1	NM_001128147.3		c.-22G>C		5_prime_UTR	Exon 1 of 15	NP_001121619.1	P21359-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NF1	ENST00000358273.9	TSL:1 MANE Select	c.-22G>C		5_prime_UTR	Exon 1 of 58	ENSP00000351015.4	P21359-1
	NF1	ENST00000356175.7	TSL:1	c.-22G>C		5_prime_UTR	Exon 1 of 57	ENSP00000348498.3	P21359-2
	NF1	ENST00000431387.8	TSL:1	c.-22G>C		5_prime_UTR	Exon 1 of 15	ENSP00000412921.4	P21359-5

Frequencies

GnomAD3 genomes AF: 0.00384 AC: 583 AN: 151754 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00347

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00396

Gnomad FIN AF: 0.00633

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00596

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.00383 AC: 502 AN: 131034 AF XY: 0.00408

Gnomad AFR exome AF: 0.000622

Gnomad AMR exome AF: 0.00164

Gnomad ASJ exome AF: 0.00186

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00643

Gnomad NFE exome AF: 0.00631

Gnomad OTH exome AF: 0.00547

GnomAD4 exome AF: 0.00622 AC: 8601 AN: 1382934 Hom.: 33 Cov.: 32 AF XY: 0.00626 AC XY: 4269 AN XY: 682374

African (AFR) AF: 0.000699 AC: 22 AN: 31478

American (AMR) AF: 0.00163 AC: 58 AN: 35620

Ashkenazi Jewish (ASJ) AF: 0.00195 AC: 49 AN: 25118

East Asian (EAS) AF: 0.00 AC: 0 AN: 35700

South Asian (SAS) AF: 0.00334 AC: 264 AN: 79050

European-Finnish (FIN) AF: 0.00676 AC: 247 AN: 36512

Middle Eastern (MID) AF: 0.00467 AC: 19 AN: 4072

European-Non Finnish (NFE) AF: 0.00710 AC: 7651 AN: 1077728

Other (OTH) AF: 0.00505 AC: 291 AN: 57656

GnomAD4 genome AF: 0.00384 AC: 583 AN: 151872 Hom.: 1 Cov.: 30 AF XY: 0.00362 AC XY: 269 AN XY: 74230

African (AFR) AF: 0.00133 AC: 55 AN: 41420

American (AMR) AF: 0.00124 AC: 19 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00347 AC: 12 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00396 AC: 19 AN: 4798

European-Finnish (FIN) AF: 0.00633 AC: 67 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00597 AC: 405 AN: 67892

Other (OTH) AF: 0.00285 AC: 6 AN: 2106

Alfa AF: 0.00202 Hom.: 2

Bravo AF: 0.00358

Asia WGS AF: 0.000867 AC: 3 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Neurofibromatosis, type 1 (2)
-	-	1	Café-au-lait macules with pulmonary stenosis (1)
-	-	1	Neurofibromatosis-Noonan syndrome (1)
-	-	1	Neurofibromatosis, familial spinal (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Benign	0.90
PhyloP100		1.4
PromoterAI		0.21	Neutral
Mutation Taster		=296/4	polymorphism

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: rs556823296; hg19: chr17-29422306;