17-3802217-C-G

Position:

• chr17-3802217-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001114118.3(NCBP3):​c.*10827G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0224 in 152,084 control chromosomes in the GnomAD database, including 52 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 0.022 (52 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NCBP3 NM_001114118.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351

Genes affected

NCBP3 (HGNC:24612): (nuclear cap binding subunit 3) Enables RNA 7-methylguanosine cap binding activity and mRNA binding activity. Involved in defense response to virus. Located in cytoplasm and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

NCBP3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0224 (3414/152084) while in subpopulation SAS AF= 0.0258 (124/4804). AF 95% confidence interval is 0.0226. There are 52 homozygotes in gnomad4. There are 1760 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 52 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCBP3	NM_001114118.3	c.*10827G>C		3_prime_UTR_variant	13/13	ENST00000389005.6	NP_001107590.1
NCBP3	NM_001398494.1	c.*10329G>C		3_prime_UTR_variant	14/14		NP_001385423.1
NCBP3	XR_007065313.1	n.2239G>C		non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCBP3	ENST00000389005.6	c.*10827G>C		3_prime_UTR_variant	13/13	5	NM_001114118.3	ENSP00000373657.4
NCBP3	ENST00000572988.1	n.466G>C		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.0225 AC: 3413 AN: 151966 Hom.: 52 Cov.: 33

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0254

Gnomad FIN AF: 0.0458

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.0191

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0224 AC: 3414 AN: 152084 Hom.: 52 Cov.: 33 AF XY: 0.0237 AC XY: 1760 AN XY: 74338

Gnomad4 AFR AF: 0.0204

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.0239

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0258

Gnomad4 FIN AF: 0.0458

Gnomad4 NFE AF: 0.0236

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0215 Hom.: 5

Bravo AF: 0.0196

Asia WGS AF: 0.00924 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.52
DANN	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs16953477; hg19: chr17-3705511;