rs7510

Positions:

• chr2-182924921-C-A
• chr2-182924921-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_013436.5(NCKAP1):​c.*781G>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.613 in 151,900 control chromosomes in the GnomAD database, including 31,764 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 0.61 (31764 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: NCKAP1 NM_013436.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91

Genes affected

NCKAP1 (HGNC:7666): (NCK associated protein 1) Contributes to small GTPase binding activity. Involved in Rac protein signal transduction; positive regulation of Arp2/3 complex-mediated actin nucleation; and positive regulation of lamellipodium assembly. Located in extracellular exosome and focal adhesion. Part of SCAR complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCKAP1	NM_013436.5	c.*781G>T		3_prime_UTR_variant	31/31	ENST00000361354.9	NP_038464.1
NCKAP1	NM_205842.3	c.*781G>T		3_prime_UTR_variant	32/32		NP_995314.1
NCKAP1	XM_006712200.4	c.*781G>T		3_prime_UTR_variant	32/32		XP_006712263.1
NCKAP1	XM_006712201.4	c.*781G>T		3_prime_UTR_variant	31/31		XP_006712264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCKAP1	ENST00000361354.9	c.*781G>T		3_prime_UTR_variant	31/31	1	NM_013436.5	ENSP00000355348	P4
NCKAP1	ENST00000360982.2	c.*781G>T		3_prime_UTR_variant	32/32	1		ENSP00000354251
NCKAP1	ENST00000703824.1	c.*781G>T		3_prime_UTR_variant	32/32			ENSP00000515489
NCKAP1	ENST00000703825.1	c.*781G>T		3_prime_UTR_variant	31/31			ENSP00000515490	A1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93019 AN: 151782 Hom.: 31759 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.627

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.613 AC: 93043 AN: 151900 Hom.: 31764 Cov.: 32 AF XY: 0.618 AC XY: 45901 AN XY: 74214

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.711

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.797

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.628

Alfa AF: 0.664 Hom.: 14388

Bravo AF: 0.592

Asia WGS AF: 0.723 AC: 2508 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.88

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: rs7510; hg19: chr2-183789649;