rs1629826

Variant names:

• chr12-54515360-G-A
• rs1629826
• NM_005337.5:c.942-879G>A

Variant summary

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

The NM_005337.5(NCKAP1L):​c.942-879G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,034 control chromosomes in the GnomAD database, including 31,360 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 0.64 (31360 hom., cov: 32)
• Consequence: NCKAP1L NM_005337.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 5 publications found

Genes affected

NCKAP1L (HGNC:4862): (NCK associated protein 1 like) This gene encodes a member of the HEM family of tissue-specific transmembrane proteins which are highly conserved from invertebrates through mammals. This gene is only expressed in hematopoietic cells. The encoded protein is a part of the Scar/WAVE complex which plays an important role in regulating cell shape in both metazoans and plants. Alternatively spliced transcript variants encoding different isoforms have been found.[provided by RefSeq, May 2010]

NCKAP1L Gene-Disease associations (from GenCC):

• immunodeficiency 72 with autoinflammation

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005337.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCKAP1L	NM_005337.5	MANE Select	c.942-879G>A		intron	N/A	NP_005328.2
	NCKAP1L	NM_001184976.2		c.792-879G>A		intron	N/A	NP_001171905.1	P55160-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCKAP1L	ENST00000293373.11	TSL:1 MANE Select	c.942-879G>A		intron	N/A	ENSP00000293373.6	P55160-1
	NCKAP1L	ENST00000858319.1		c.942-879G>A		intron	N/A	ENSP00000528378.1
	NCKAP1L	ENST00000858318.1		c.942-879G>A		intron	N/A	ENSP00000528377.1

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97070 AN: 151914 Hom.: 31340 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.639 AC: 97139 AN: 152034 Hom.: 31360 Cov.: 32 AF XY: 0.639 AC XY: 47496 AN XY: 74274

African (AFR) AF: 0.624 AC: 25897 AN: 41482

American (AMR) AF: 0.704 AC: 10756 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2131 AN: 3470

East Asian (EAS) AF: 0.933 AC: 4838 AN: 5186

South Asian (SAS) AF: 0.740 AC: 3566 AN: 4818

European-Finnish (FIN) AF: 0.587 AC: 6187 AN: 10532

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.612 AC: 41580 AN: 67964

Other (OTH) AF: 0.641 AC: 1347 AN: 2102

Alfa AF: 0.623 Hom.: 63843

Bravo AF: 0.644

Asia WGS AF: 0.823 AC: 2865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.084
DANN	Benign	0.41
PhyloP100		-1.4
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: rs1629826; hg19: chr12-54909144;