rs6430390

chr2-133080663-A-Gchr2-133080663-A-T

Variant summary

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

The NM_207363.3(NCKAP5):c.341+49315T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,032 control chromosomes in the GnomAD database, including 7,203 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 0.30 (7203 hom., cov: 33)
• Consequence: NCKAP5 NM_207363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.526

Genes affected

NCKAP5 (HGNC:29847): (NCK associated protein 5) Predicted to be involved in microtubule bundle formation and microtubule depolymerization. Predicted to be active in microtubule plus-end. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCKAP5	NM_207363.3	c.341+49315T>C		intron_variant		ENST00000409261.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCKAP5	ENST00000409261.6	c.341+49315T>C		intron_variant		5	NM_207363.3	P1
NCKAP5	ENST00000409213.5	c.341+49315T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45341 AN: 151914 Hom.: 7198 Cov.: 33

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.0173

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.298 AC: 45366 AN: 152032 Hom.: 7203 Cov.: 33 AF XY: 0.292 AC XY: 21723 AN XY: 74336

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.0174

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.279

Alfa AF: 0.310 Hom.: 9667

Bravo AF: 0.291

Asia WGS AF: 0.129 AC: 449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	3.4
Dann	Benign	0.73

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: rs6430390; hg19: chr2-133838236;