chr14-26452964-T-C

Position:

• chr14-26452964-T-C

Variant summary

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

The ENST00000539517.7(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 ENST00000539517.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.72

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=-0.95).
• 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/exons	MANE	Protein	UniProt
NOVA1	NM_002515.3	c.520-4001A>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.520-4001A>G		intron_variant		1	NM_002515.3	ENSP00000438875	P1

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

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.957

Gnomad4 ASJ AF: 0.973

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.997

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.993

Gnomad4 OTH AF: 0.930

Alfa AF: 0.979 Hom.: 21507

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

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: rs178228; hg19: chr14-26922170;