rs11751998

Variant names:

• chr6-11188854-C-T
• rs11751998
• NM_006403.4:c.1906-547G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ENSG00000247925 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006403.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD9	NM_006403.4	MANE Select	c.1906-547G>A		intron	N/A	NP_006394.1	Q14511-1
	NEDD9	NM_001142393.2		c.1906-547G>A		intron	N/A	NP_001135865.1	Q14511-3
	NEDD9	NM_001271033.2		c.1459-547G>A		intron	N/A	NP_001257962.1	A0A087WUD2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD9	ENST00000379446.10	TSL:1 MANE Select	c.1906-547G>A		intron	N/A	ENSP00000368759.5	Q14511-1
	NEDD9	ENST00000448183.6	TSL:1	n.*2019-547G>A		intron	N/A	ENSP00000395237.2	D6RDV1
	NEDD9	ENST00000504387.5	TSL:2	c.1906-547G>A		intron	N/A	ENSP00000422871.1	Q14511-3

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

African (AFR) AF: 0.0389 AC: 1614 AN: 41464

American (AMR) AF: 0.0867 AC: 1323 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3470

East Asian (EAS) AF: 0.0231 AC: 120 AN: 5188

South Asian (SAS) AF: 0.0625 AC: 301 AN: 4818

European-Finnish (FIN) AF: 0.196 AC: 2064 AN: 10534

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12410 AN: 67982

Other (OTH) AF: 0.103 AC: 218 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.76
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11751998; hg19: chr6-11189087;