6-11271759-T-C

Variant names:

• chr6-11271759-T-C
• rs16871186
• ENST00000448183.6:n.106+33307A>G

Variant summary

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

The NM_001142393.2(NEDD9):​c.12+34233A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0817 in 152,298 control chromosomes in the GnomAD database, including 593 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 0.082 (593 hom., cov: 32)
  • Exomes 𝑓: 0.063 (0 hom.)
• Consequence: NEDD9 NM_001142393.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEDD9	NM_001142393.2	c.12+34233A>G		intron_variant	Intron 2 of 7		NP_001135865.1
NEDD9	NR_073131.1	n.468+33307A>G		intron_variant	Intron 3 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEDD9	ENST00000448183.6	n.106+33307A>G		intron_variant	Intron 3 of 9	1		ENSP00000395237.2
NEDD9	ENST00000504387.5	c.12+34233A>G		intron_variant	Intron 2 of 7	2		ENSP00000422871.1
NEDD9	ENST00000397378.7	c.12+34233A>G		intron_variant	Intron 3 of 3	3		ENSP00000380534.3

Frequencies

GnomAD3 genomes AF: 0.0816 AC: 12423 AN: 152166 Hom.: 587 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0749

Gnomad ASJ AF: 0.0585

Gnomad EAS AF: 0.0423

Gnomad SAS AF: 0.0453

Gnomad FIN AF: 0.0604

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0550

Gnomad OTH AF: 0.0869

GnomAD4 exome AF: 0.0625 AC: 1 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.0833

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0817 AC: 12447 AN: 152282 Hom.: 593 Cov.: 32 AF XY: 0.0818 AC XY: 6095 AN XY: 74466

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0748

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.0422

Gnomad4 SAS AF: 0.0458

Gnomad4 FIN AF: 0.0604

Gnomad4 NFE AF: 0.0551

Gnomad4 OTH AF: 0.0860

Alfa AF: 0.0364 Hom.: 34

Bravo AF: 0.0870

Asia WGS AF: 0.0610 AC: 213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16871186; hg19: chr6-11271992;