Genetic Variant NM_001291999.2:c.-18-27917G>C (chr3-136900067-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.100

Publications

14 publications found

Variant links:

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]

NCK1 links:

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

RAD51AP1P1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 link	c.-18-27917G>C		intron_variant	Intron 1 of 3	ENST00000481752.6	NP_001278928.1	P16333-1A0A0S2Z4Y3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCK1	ENST00000481752.6 link	c.-18-27917G>C		intron_variant	Intron 1 of 3	5	NM_001291999.2	ENSP00000417273.1		P16333-1

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24706

AN:

152058

Hom.:

2668

Cov.:

show subpopulations

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.:

AF XY:

0.216

AC XY:

44837

AN XY:

207226

show subpopulations

African (AFR)

AF:

0.0386

AC:

417

AN:

10792

American (AMR)

AF:

0.101

AC:

1801

AN:

17846

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

2473

AN:

10352

East Asian (EAS)

AF:

0.000480

AC:

AN:

22896

South Asian (SAS)

AF:

0.245

AC:

11291

AN:

46164

European-Finnish (FIN)

AF:

0.226

AC:

7346

AN:

32446

Middle Eastern (MID)

AF:

0.270

AC:

385

AN:

1424

European-Non Finnish (NFE)

AF:

0.239

AC:

52093

AN:

217650

Other (OTH)

AF:

0.205

AC:

4114

AN:

20076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2863

5726

8590

11453

14316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

226

452

678

904

1130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.162

AC:

24695

AN:

152176

Hom.:

2667

Cov.:

AF XY:

0.162

AC XY:

12052

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0398

AC:

1653

AN:

41534

American (AMR)

AF:

0.132

AC:

2011

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

838

AN:

3470

East Asian (EAS)

AF:

0.00212

AC:

AN:

5184

South Asian (SAS)

AF:

0.222

AC:

1071

AN:

4820

European-Finnish (FIN)

AF:

0.228

AC:

2411

AN:

10582

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.238

AC:

16155

AN:

67982

Other (OTH)

AF:

0.158

AC:

334

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

999

1998

2996

3995

4994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

282

564

846

1128

1410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.61

PhyloP100

0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over