rs16871253

Positions:

• chr6-11322403-G-A

Variant summary

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

The ENST00000448183.6(NEDD9):​c.-152-16248C>T variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0638 in 152,186 control chromosomes in the GnomAD database, including 338 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 0.064 (338 hom., cov: 32)
• Consequence: NEDD9 ENST00000448183.6 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

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]

LOC105374925 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105374925	XR_001743967.2	n.8117+1641G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEDD9	ENST00000448183.6	c.-152-16248C>T		intron_variant, NMD_transcript_variant		1		ENSP00000395237
NEDD9	ENST00000397378.7	c.-153+12098C>T		intron_variant		3		ENSP00000380534
NEDD9	ENST00000504387.5	c.-152-16248C>T		intron_variant		2		ENSP00000422871	A1

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9714 AN: 152068 Hom.: 336 Cov.: 32

Gnomad AFR AF: 0.0769

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0698

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0584

Gnomad OTH AF: 0.0737

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

GnomAD4 genome AF: 0.0638 AC: 9716 AN: 152186 Hom.: 338 Cov.: 32 AF XY: 0.0632 AC XY: 4700 AN XY: 74416

Gnomad4 AFR AF: 0.0768

Gnomad4 AMR AF: 0.0697

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.0473

Gnomad4 SAS AF: 0.0435

Gnomad4 FIN AF: 0.0607

Gnomad4 NFE AF: 0.0584

Gnomad4 OTH AF: 0.0729

Alfa AF: 0.0605 Hom.: 435

Bravo AF: 0.0676

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16871253; hg19: chr6-11322636;