chr3-136900067-G-C

Variant names:

• chr3-136900067-G-C
• rs9867325
• NM_001291999.2:c.-18-27917G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291999.2(NCK1):​c.-18-27917G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 531,822 control chromosomes in the GnomAD database, including 12,162 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 0.16 (2667 hom., cov: 32)
  • Exomes 𝑓: 0.21 (9495 hom.)
• Consequence: NCK1 NM_001291999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100

Genes affected

NCK1 (HGNC:7664): (NCK adaptor protein 1) The protein encoded by this gene is one of the signaling and transforming proteins containing Src homology 2 and 3 (SH2 and SH3) domains. It is located in the cytoplasm and is an adaptor protein involved in transducing signals from receptor tyrosine kinases to downstream signal recipients such as RAS. Alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Jun 2010]

RAD51AP1P1 (HGNC:49646): (RAD51AP1 pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCK1	NM_001291999.2	c.-18-27917G>C		intron_variant	Intron 1 of 3	ENST00000481752.6	NP_001278928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCK1	ENST00000481752.6	c.-18-27917G>C		intron_variant	Intron 1 of 3	5	NM_001291999.2	ENSP00000417273.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24706 AN: 152058 Hom.: 2668 Cov.: 32

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.211 AC: 79931 AN: 379646 Hom.: 9495 Cov.: 0 AF XY: 0.216 AC XY: 44837 AN XY: 207226

Gnomad4 AFR exome AF: 0.0386

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.000480

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.226

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.162 AC: 24695 AN: 152176 Hom.: 2667 Cov.: 32 AF XY: 0.162 AC XY: 12052 AN XY: 74398

Gnomad4 AFR AF: 0.0398

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.158

Alfa AF: 0.117 Hom.: 213

Bravo AF: 0.148

Asia WGS AF: 0.0870 AC: 304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9867325; hg19: chr3-136618909;