rs16871204

Positions:

• chr6-11277292-T-C

Variant summary

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

The ENST00000448183.6(NEDD9):​c.106+27774A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 152,224 control chromosomes in the GnomAD database, including 379 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 0.069 (379 hom., cov: 32)
• Consequence: NEDD9 ENST00000448183.6 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEDD9	NM_001142393.2	c.12+28700A>G		intron_variant
NEDD9	NR_073131.1	n.468+27774A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEDD9	ENST00000448183.6	c.106+27774A>G		intron_variant, NMD_transcript_variant		1
NEDD9	ENST00000397378.7	c.12+28700A>G		intron_variant		3
NEDD9	ENST00000504387.5	c.12+28700A>G		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.0693 AC: 10538 AN: 152106 Hom.: 375 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.0419

Gnomad SAS AF: 0.0453

Gnomad FIN AF: 0.0606

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.0755

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

GnomAD4 genome AF: 0.0693 AC: 10551 AN: 152224 Hom.: 379 Cov.: 32 AF XY: 0.0701 AC XY: 5218 AN XY: 74432

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0666

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.0418

Gnomad4 SAS AF: 0.0458

Gnomad4 FIN AF: 0.0606

Gnomad4 NFE AF: 0.0549

Gnomad4 OTH AF: 0.0747

Alfa AF: 0.0598 Hom.: 82

Bravo AF: 0.0730

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.9
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16871204; hg19: chr6-11277525;