rs178208

Positions:

• chr14-26485260-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002515.3(NOVA1):​c.281-5117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 151,866 control chromosomes in the GnomAD database, including 31,591 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 0.60 (31591 hom., cov: 31)
• Consequence: NOVA1 NM_002515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOVA1	NM_002515.3	c.281-5117A>G		intron_variant		ENST00000539517.7	NP_002506.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOVA1	ENST00000539517.7	c.281-5117A>G		intron_variant		1	NM_002515.3	ENSP00000438875.2

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91759 AN: 151750 Hom.: 31594 Cov.: 31

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.604 AC: 91762 AN: 151866 Hom.: 31591 Cov.: 31 AF XY: 0.612 AC XY: 45455 AN XY: 74228

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.749

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.632

Alfa AF: 0.673 Hom.: 4608

Bravo AF: 0.585

Asia WGS AF: 0.615 AC: 2141 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.90
DANN	Benign	0.40

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: rs178208; hg19: chr14-26954466;