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GeneBe

6-11185630-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_006403.4(NEDD9):c.2037C>T(p.Pro679=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000423 in 1,614,180 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00041 ( 3 hom. )

Consequence

NEDD9
NM_006403.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.93
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-11185630-G-A is Benign according to our data. Variant chr6-11185630-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656226.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.93 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 79 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NEDD9NM_006403.4 linkuse as main transcriptc.2037C>T p.Pro679= synonymous_variant 7/7 ENST00000379446.10
NEDD9NM_001142393.2 linkuse as main transcriptc.2037C>T p.Pro679= synonymous_variant 8/8
NEDD9NM_001271033.2 linkuse as main transcriptc.1590C>T p.Pro530= synonymous_variant 6/6
NEDD9NR_073131.1 linkuse as main transcriptn.2644C>T non_coding_transcript_exon_variant 10/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NEDD9ENST00000379446.10 linkuse as main transcriptc.2037C>T p.Pro679= synonymous_variant 7/71 NM_006403.4 P4Q14511-1
ENST00000500636.2 linkuse as main transcriptn.175+412G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000519
AC:
79
AN:
152180
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000555
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.0101
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000220
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000718
AC:
179
AN:
249284
Hom.:
0
AF XY:
0.000734
AC XY:
99
AN XY:
134938
show subpopulations
Gnomad AFR exome
AF:
0.000677
Gnomad AMR exome
AF:
0.000463
Gnomad ASJ exome
AF:
0.00764
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000511
Gnomad OTH exome
AF:
0.00180
GnomAD4 exome
AF:
0.000413
AC:
604
AN:
1461882
Hom.:
3
Cov.:
37
AF XY:
0.000425
AC XY:
309
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.000627
Gnomad4 AMR exome
AF:
0.000559
Gnomad4 ASJ exome
AF:
0.00731
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000244
Gnomad4 OTH exome
AF:
0.00116
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000519
AC:
79
AN:
152298
Hom.:
0
Cov.:
33
AF XY:
0.000470
AC XY:
35
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.000553
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.0101
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000221
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00103
Hom.:
0
Bravo
AF:
0.000669
EpiCase
AF:
0.000654
EpiControl
AF:
0.000830

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2022NEDD9: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
Cadd
Benign
0.21
Dann
Benign
0.81
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144637323; hg19: chr6-11185863; API