14-26452964-T-C

Variant names:

• chr14-26452964-T-C
• rs178228
• NM_002515.3:c.520-4001A>G

Variant summary

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

The NM_002515.3(NOVA1):​c.520-4001A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.924 in 152,188 control chromosomes in the GnomAD database, including 65,750 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 0.92 (65750 hom., cov: 31)
• Consequence: NOVA1 NM_002515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.72
• Publications: 0 publications found

Genes affected

NOVA1 (HGNC:7886): (NOVA alternative splicing regulator 1) This gene encodes a neuron-specific RNA-binding protein, a member of the Nova family of paraneoplastic disease antigens, that is recognized and inhibited by paraneoplastic antibodies. These antibodies are found in the sera of patients with paraneoplastic opsoclonus-ataxia, breast cancer, and small cell lung cancer. Alternatively spliced transcripts encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOVA1	NM_002515.3	c.520-4001A>G		intron_variant	Intron 4 of 4	ENST00000539517.7	NP_002506.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOVA1	ENST00000539517.7	c.520-4001A>G		intron_variant	Intron 4 of 4	1	NM_002515.3	ENSP00000438875.2

Frequencies

GnomAD3 genomes AF: 0.924 AC: 140503 AN: 152070 Hom.: 65734 Cov.: 31

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.957

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.997

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.929

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

GnomAD4 genome AF: 0.924 AC: 140565 AN: 152188 Hom.: 65750 Cov.: 31 AF XY: 0.925 AC XY: 68880 AN XY: 74440

African (AFR) AF: 0.754 AC: 31291 AN: 41478

American (AMR) AF: 0.957 AC: 14638 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 3378 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5160 AN: 5160

South Asian (SAS) AF: 0.997 AC: 4818 AN: 4832

European-Finnish (FIN) AF: 0.999 AC: 10606 AN: 10618

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.993 AC: 67532 AN: 68016

Other (OTH) AF: 0.930 AC: 1966 AN: 2114

Alfa AF: 0.976 Hom.: 25453

Bravo AF: 0.914

Asia WGS AF: 0.980 AC: 3404 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.66
PhyloP100		-3.7
Mutation Taster		=100/0	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: rs178228; hg19: chr14-26922170;