6-11189970-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_006403.4(NEDD9):c.1899C>T(p.His633=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,515,780 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (6 hom.)
• Consequence: NEDD9 NM_006403.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.59

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 6-11189970-G-A is Benign according to our data. Variant chr6-11189970-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 710685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.59 with no splicing effect.
• BS2: High AC in GnomAd at 199 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEDD9	NM_006403.4	c.1899C>T	p.His633=	synonymous_variant	5/7	ENST00000379446.10
NEDD9	NM_001142393.2	c.1899C>T	p.His633=	synonymous_variant	6/8
NEDD9	NM_001271033.2	c.1452C>T	p.His484=	synonymous_variant	4/6
NEDD9	NR_073131.1	n.2506C>T		non_coding_transcript_exon_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEDD9	ENST00000379446.10	c.1899C>T	p.His633=	synonymous_variant	5/7	1	NM_006403.4	P4
	ENST00000500636.2	n.175+4752G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 199 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00157 AC: 276 AN: 176048 Hom.: 0 AF XY: 0.00170 AC XY: 157 AN XY: 92428

Gnomad AFR exome AF: 0.0000649

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000625

Gnomad FIN exome AF: 0.000182

Gnomad NFE exome AF: 0.00195

Gnomad OTH exome AF: 0.00221

GnomAD4 exome AF: 0.00134 AC: 1828 AN: 1363458 Hom.: 6 Cov.: 29 AF XY: 0.00140 AC XY: 933 AN XY: 667364

Gnomad4 AFR exome AF: 0.000331

Gnomad4 AMR exome AF: 0.00208

Gnomad4 ASJ exome AF: 0.0108

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000984

Gnomad4 FIN exome AF: 0.000102

Gnomad4 NFE exome AF: 0.00122

Gnomad4 OTH exome AF: 0.00255

GnomAD4 genome AF: 0.00131 AC: 199 AN: 152322 Hom.: 0 Cov.: 32 AF XY: 0.00121 AC XY: 90 AN XY: 74484

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00979

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00160

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00114 Hom.: 0

Bravo AF: 0.00154

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	NEDD9: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Apr 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	7.0
Dann	Benign	0.75
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

Other links and lift over

dbSNP: rs146864079; hg19: chr6-11190203;