rs16847549

Positions:

• chr2-133088899-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_207363.3(NCKAP5):​c.341+41079C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 152,078 control chromosomes in the GnomAD database, including 34 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 0.012 (34 hom., cov: 32)
• Consequence: NCKAP5 NM_207363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.477

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=-0.84).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1787/152078) while in subpopulation AFR AF= 0.04 (1660/41482). AF 95% confidence interval is 0.0384. There are 34 homozygotes in gnomad4. There are 873 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCKAP5	NM_207363.3	c.341+41079C>T		intron_variant		ENST00000409261.6	NP_997246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCKAP5	ENST00000409261.6	c.341+41079C>T		intron_variant		5	NM_207363.3	ENSP00000387128.1
NCKAP5	ENST00000409213.5	c.341+41079C>T		intron_variant		5		ENSP00000386952.1

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1778 AN: 151960 Hom.: 34 Cov.: 32

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00668

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000947

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.0110

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

GnomAD4 genome AF: 0.0118 AC: 1787 AN: 152078 Hom.: 34 Cov.: 32 AF XY: 0.0117 AC XY: 873 AN XY: 74336

Gnomad4 AFR AF: 0.0400

Gnomad4 AMR AF: 0.00667

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000947

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0102 Hom.: 4

Bravo AF: 0.0138

Asia WGS AF: 0.00231 AC: 8 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.6
DANN	Benign	0.64

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: rs16847549; hg19: chr2-133846472;