17-82049846-G-C

Variant names:

• chr17-82049846-G-C
• rs200651785
• NM_002917.2:c.663-4C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002917.2(RFNG):​c.663-4C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000625 in 1,604,350 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00040 (1 hom., cov: 35)
  • Exomes 𝑓: 0.00065 (1 hom.)
• Consequence: RFNG NM_002917.2 splice_region, intron
• Scores: Splicing: ADA: 0.00006965
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.681
• Publications: 0 publications found

Genes affected

RFNG (HGNC:9974): (RFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase) Predicted to enable O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase activity. Predicted to be involved in regulation of Notch signaling pathway. Predicted to act upstream of or within positive regulation of Notch signaling pathway and positive regulation of protein binding activity. Predicted to be integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-82049846-G-C is Benign according to our data. Variant chr17-82049846-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2648481.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 61 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002917.2. 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
	RFNG	NM_002917.2	MANE Select	c.663-4C>G		splice_region intron	N/A	NP_002908.1	Q9Y644

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFNG	ENST00000310496.9	TSL:2 MANE Select	c.663-4C>G		splice_region intron	N/A	ENSP00000307971.4	Q9Y644
	RFNG	ENST00000582478.5	TSL:1	n.1723C>G		non_coding_transcript_exon	Exon 3 of 4
	RFNG	ENST00000580793.5	TSL:1	n.598-4C>G		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000401 AC: 61 AN: 152226 Hom.: 1 Cov.: 35

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000263 AC: 63 AN: 239800 AF XY: 0.000291

Gnomad AFR exome AF: 0.000324

Gnomad AMR exome AF: 0.0000605

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000278

Gnomad FIN exome AF: 0.0000480

Gnomad NFE exome AF: 0.000426

Gnomad OTH exome AF: 0.000518

GnomAD4 exome AF: 0.000648 AC: 941 AN: 1452006 Hom.: 1 Cov.: 32 AF XY: 0.000621 AC XY: 448 AN XY: 721726

African (AFR) AF: 0.000302 AC: 10 AN: 33126

American (AMR) AF: 0.0000461 AC: 2 AN: 43362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25538

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39580

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85478

European-Finnish (FIN) AF: 0.000174 AC: 9 AN: 51786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.000800 AC: 886 AN: 1107472

Other (OTH) AF: 0.000417 AC: 25 AN: 59944

GnomAD4 genome AF: 0.000400 AC: 61 AN: 152344 Hom.: 1 Cov.: 35 AF XY: 0.000336 AC XY: 25 AN XY: 74492

African (AFR) AF: 0.000168 AC: 7 AN: 41576

American (AMR) AF: 0.000131 AC: 2 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.000720 AC: 49 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000213 Hom.: 0

Bravo AF: 0.000423

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.37
DANN	Benign	0.73
PhyloP100		-0.68
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000070
dbscSNV1_RF	Benign	0.020
SpliceAI score (max)		0.010		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: rs200651785; hg19: chr17-80007722;