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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000448183.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD9	NM_001142393.2		c.12+34233A>G		intron	N/A	NP_001135865.1
	NEDD9	NR_073131.1		n.468+33307A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NEDD9	ENST00000448183.6	TSL:1	n.106+33307A>G	intron	N/A	ENSP00000395237.2
NEDD9	ENST00000504634.5	TSL:3	n.432A>G	non_coding_transcript_exon	Exon 3 of 3
NEDD9	ENST00000504387.5	TSL:2	c.12+34233A>G	intron	N/A	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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over