rs178208

Variant names:

• chr14-26485260-T-C
• rs178208
• NM_002515.3:c.281-5117A>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.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
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002515.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOVA1	NM_002515.3	MANE Select	c.281-5117A>G		intron	N/A	NP_002506.2
	NOVA1	NM_001366392.2		c.278-5117A>G		intron	N/A	NP_001353321.1
	NOVA1	NM_006489.3		c.281-5117A>G		intron	N/A	NP_006480.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOVA1	ENST00000539517.7	TSL:1 MANE Select	c.281-5117A>G		intron	N/A	ENSP00000438875.2
	NOVA1	ENST00000483536.6	TSL:1	n.*17-5117A>G		intron	N/A	ENSP00000448956.1
	NOVA1	ENST00000465357.6	TSL:3	c.281-5117A>G		intron	N/A	ENSP00000447391.1

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

African (AFR) AF: 0.246 AC: 10197 AN: 41396

American (AMR) AF: 0.708 AC: 10816 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2229 AN: 3468

East Asian (EAS) AF: 0.596 AC: 3062 AN: 5134

South Asian (SAS) AF: 0.749 AC: 3599 AN: 4802

European-Finnish (FIN) AF: 0.809 AC: 8532 AN: 10552

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51084 AN: 67932

Other (OTH) AF: 0.632 AC: 1332 AN: 2108

Alfa AF: 0.656 Hom.: 4633

Bravo AF: 0.585

Asia WGS AF: 0.615 AC: 2141 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.90
DANN	Benign	0.40
PhyloP100		-0.021
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: rs178208; hg19: chr14-26954466;