rs1629826

Positions:

• chr12-54515360-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCKAP1L	NM_005337.5	c.942-879G>A		intron_variant		ENST00000293373.11
NCKAP1L	NM_001184976.2	c.792-879G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCKAP1L	ENST00000293373.11	c.942-879G>A		intron_variant		1	NM_005337.5	P1
NCKAP1L	ENST00000545638.2	c.792-879G>A		intron_variant		2
NCKAP1L	ENST00000548221.5	c.942-879G>A		intron_variant, NMD_transcript_variant		2
NCKAP1L	ENST00000552211.5	n.438-879G>A		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.933

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.641

Alfa AF: 0.621 Hom.: 43651

Bravo AF: 0.644

Asia WGS AF: 0.823 AC: 2865 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.084
DANN	Benign	0.41

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: rs1629826; hg19: chr12-54909144;