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GeneBe

6-11190126-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.1743C>T(p.His581=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,613,398 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 12 hom. )

Consequence

NEDD9
NM_006403.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.08
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=-0.88).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-11190126-G-A is Benign according to our data. Variant chr6-11190126-G-A is described in ClinVar as [Benign]. Clinvar id is 785803.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=-2.08 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 251 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NEDD9NM_006403.4 linkuse as main transcriptc.1743C>T p.His581= synonymous_variant 5/7 ENST00000379446.10
NEDD9NM_001142393.2 linkuse as main transcriptc.1743C>T p.His581= synonymous_variant 6/8
NEDD9NM_001271033.2 linkuse as main transcriptc.1296C>T p.His432= synonymous_variant 4/6
NEDD9NR_073131.1 linkuse as main transcriptn.2350C>T non_coding_transcript_exon_variant 8/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NEDD9ENST00000379446.10 linkuse as main transcriptc.1743C>T p.His581= synonymous_variant 5/71 NM_006403.4 P4Q14511-1
ENST00000500636.2 linkuse as main transcriptn.175+4908G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00165
AC:
251
AN:
152194
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00360
Gnomad ASJ
AF:
0.0138
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00394
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.00157
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00250
AC:
628
AN:
250874
Hom.:
2
AF XY:
0.00270
AC XY:
366
AN XY:
135562
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.00385
Gnomad ASJ exome
AF:
0.0114
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00333
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00202
Gnomad OTH exome
AF:
0.00686
GnomAD4 exome
AF:
0.00164
AC:
2403
AN:
1461086
Hom.:
12
Cov.:
30
AF XY:
0.00176
AC XY:
1281
AN XY:
726752
show subpopulations
Gnomad4 AFR exome
AF:
0.000538
Gnomad4 AMR exome
AF:
0.00338
Gnomad4 ASJ exome
AF:
0.0120
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00412
Gnomad4 FIN exome
AF:
0.0000375
Gnomad4 NFE exome
AF:
0.00117
Gnomad4 OTH exome
AF:
0.00277
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00165
AC:
251
AN:
152312
Hom.:
1
Cov.:
32
AF XY:
0.00160
AC XY:
119
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.00360
Gnomad4 ASJ
AF:
0.0138
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00394
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00157
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00249
Hom.:
0
Bravo
AF:
0.00178
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00327
EpiControl
AF:
0.00338

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
Cadd
Benign
0.11
Dann
Benign
0.59
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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: rs143967808; hg19: chr6-11190359; API