2-133605461-T-C

Variant names:

• chr2-133605461-T-C
• rs7588567
• ENST00000830630.1:n.164+1366T>C

Variant summary

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

The ENST00000830630.1(ENSG00000308040):​n.164+1366T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,880 control chromosomes in the GnomAD database, including 14,241 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 0.43 (14241 hom., cov: 31)
• Consequence: ENSG00000308040 ENST00000830630.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 13 publications found

Genes affected

ENSG00000308040 (HGNC:):

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCKAP5	XM_005263660.5	c.-62+35896A>G		intron_variant	Intron 1 of 17		XP_005263717.1
NCKAP5	XM_011511099.4	c.-130+35896A>G		intron_variant	Intron 1 of 18		XP_011509401.1
NCKAP5	XM_011511100.4	c.-129-46344A>G		intron_variant	Intron 1 of 18		XP_011509402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000308040	ENST00000830630.1	n.164+1366T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65177 AN: 151762 Hom.: 14220 Cov.: 31

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.430 AC: 65236 AN: 151880 Hom.: 14241 Cov.: 31 AF XY: 0.431 AC XY: 31997 AN XY: 74230

African (AFR) AF: 0.394 AC: 16294 AN: 41392

American (AMR) AF: 0.447 AC: 6824 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1138 AN: 3470

East Asian (EAS) AF: 0.630 AC: 3241 AN: 5144

South Asian (SAS) AF: 0.455 AC: 2190 AN: 4810

European-Finnish (FIN) AF: 0.455 AC: 4796 AN: 10540

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29379 AN: 67940

Other (OTH) AF: 0.419 AC: 885 AN: 2112

Alfa AF: 0.419 Hom.: 13456

Bravo AF: 0.427

Asia WGS AF: 0.554 AC: 1928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.61
PhyloP100		-0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7588567; hg19: chr2-134363032;