rs6749561

Variant names:

• chr2-133242492-A-G
• rs6749561
• NM_207363.3:c.144-28713T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207363.3(NCKAP5):​c.144-28713T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,032 control chromosomes in the GnomAD database, including 4,841 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 0.24 (4841 hom., cov: 32)
• Consequence: NCKAP5 NM_207363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.954
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCKAP5	NM_207363.3	c.144-28713T>C		intron_variant	Intron 4 of 19	ENST00000409261.6	NP_997246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCKAP5	ENST00000409261.6	c.144-28713T>C		intron_variant	Intron 4 of 19	5	NM_207363.3	ENSP00000387128.1
NCKAP5	ENST00000427594.5	c.129-28713T>C		intron_variant	Intron 2 of 4	1		ENSP00000399070.1
NCKAP5	ENST00000409213.5	c.144-28713T>C		intron_variant	Intron 4 of 17	5		ENSP00000386952.1
NCKAP5	ENST00000358991.4	c.144-28713T>C		intron_variant	Intron 3 of 3	5		ENSP00000351882.4

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36605 AN: 151914 Hom.: 4822 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.241 AC: 36670 AN: 152032 Hom.: 4841 Cov.: 32 AF XY: 0.240 AC XY: 17859 AN XY: 74324

African (AFR) AF: 0.362 AC: 15007 AN: 41424

American (AMR) AF: 0.196 AC: 3000 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 477 AN: 3466

East Asian (EAS) AF: 0.176 AC: 911 AN: 5174

South Asian (SAS) AF: 0.249 AC: 1200 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2080 AN: 10556

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13177 AN: 67980

Other (OTH) AF: 0.228 AC: 482 AN: 2114

Alfa AF: 0.210 Hom.: 10244

Bravo AF: 0.248

Asia WGS AF: 0.260 AC: 903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.54
DANN	Benign	0.58
PhyloP100		-0.95
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: rs6749561; hg19: chr2-134000064;