Genetic Variant NEDD9:n.106+33307A>G (chr6-11271759-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000448183.6(NEDD9):n.106+33307A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0817 in 152,298 control chromosomes in the GnomAD database, including 593 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 0.082 ( 593 hom., cov: 32)

Exomes 𝑓: 0.063 ( 0 hom. )

Consequence

NEDD9
ENST00000448183.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.439

Publications

5 publications found

Variant links:

Genes affected

NEDD9 (HGNC:7733): (neural precursor cell expressed, developmentally down-regulated 9) The protein encoded by this gene is a member of the CRK-associated substrates family. Members of this family are adhesion docking molecules that mediate protein-protein interactions for signal transduction pathways. This protein is a focal adhesion protein that acts as a scaffold to regulate signaling complexes important in cell attachment, migration and invasion as well as apoptosis and the cell cycle. This protein has also been reported to have a role in cancer metastasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

NEDD9 links:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEDD9	NM_001142393.2 link	c.12+34233A>G		intron_variant	Intron 2 of 7		NP_001135865.1
NEDD9	NR_073131.1 link	n.468+33307A>G		intron_variant	Intron 3 of 9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
NEDD9	ENST00000448183.6 link	n.106+33307A>G	intron_variant	Intron 3 of 9	1	ENSP00000395237.2
NEDD9	ENST00000504634.5 link	n.432A>G	non_coding_transcript_exon_variant	Exon 3 of 3	3
NEDD9	ENST00000504387.5 link	c.12+34233A>G	intron_variant	Intron 2 of 7	2	ENSP00000422871.1

Frequencies

GnomAD3 genomes

AF:

0.0816

AC:

12423

AN:

152166

Hom.:

587

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0749

Gnomad ASJ

AF:

0.0585

Gnomad EAS

AF:

0.0423

Gnomad SAS

AF:

0.0453

Gnomad FIN

AF:

0.0604

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.0550

Gnomad OTH

AF:

0.0869

GnomAD4 exome

AF:

0.0625

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0833

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0833

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0817

AC:

12447

AN:

152282

Hom.:

593

Cov.:

AF XY:

0.0818

AC XY:

6095

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.145

AC:

6036

AN:

41534

American (AMR)

AF:

0.0748

AC:

1144

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0585

AC:

203

AN:

3468

East Asian (EAS)

AF:

0.0422

AC:

219

AN:

5192

South Asian (SAS)

AF:

0.0458

AC:

221

AN:

4830

European-Finnish (FIN)

AF:

0.0604

AC:

641

AN:

10612

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0551

AC:

3745

AN:

68024

Other (OTH)

AF:

0.0860

AC:

182

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

575

1150

1725

2300

2875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0392

Hom.:

Bravo

AF:

0.0870

Asia WGS

AF:

0.0610

AC:

213

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.0

(source)

DANN

Benign

0.48

PhyloP100

-0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over