rs11751998

chr6-11188854-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006403.4(NEDD9):c.1906-547G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,040 control chromosomes in the GnomAD database, including 1,497 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 0.12 (1497 hom., cov: 32)
• Consequence: NEDD9 NM_006403.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.649

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEDD9	NM_006403.4	c.1906-547G>A		intron_variant		ENST00000379446.10
NEDD9	NM_001142393.2	c.1906-547G>A		intron_variant
NEDD9	NM_001271033.2	c.1459-547G>A		intron_variant
NEDD9	NR_073131.1	n.2513-547G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEDD9	ENST00000379446.10	c.1906-547G>A		intron_variant		1	NM_006403.4	P4
	ENST00000500636.2	n.175+3636C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18435 AN: 151928 Hom.: 1499 Cov.: 32

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0868

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.0634

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.104

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.121 AC: 18437 AN: 152040 Hom.: 1497 Cov.: 32 AF XY: 0.119 AC XY: 8875 AN XY: 74310

Gnomad4 AFR AF: 0.0389

Gnomad4 AMR AF: 0.0867

Gnomad4 ASJ AF: 0.0879

Gnomad4 EAS AF: 0.0231

Gnomad4 SAS AF: 0.0625

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.103

Alfa AF: 0.148 Hom.: 305

Bravo AF: 0.107

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.34
Dann	Benign	0.76

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: rs11751998; hg19: chr6-11189087;