rs11961171

chr6-11275795-G-A

Variant summary

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

The ENST00000448183.6(NEDD9):c.106+29271C>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 0.0818 in 152,148 control chromosomes in the GnomAD database, including 598 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 (598 hom., cov: 32)
• Consequence: NEDD9 ENST00000448183.6 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEDD9	NM_001142393.2	c.12+30197C>T		intron_variant
NEDD9	NR_073131.1	n.468+29271C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEDD9	ENST00000448183.6	c.106+29271C>T		intron_variant, NMD_transcript_variant		1
NEDD9	ENST00000397378.7	c.12+30197C>T		intron_variant		3
NEDD9	ENST00000504387.5	c.12+30197C>T		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.0817 AC: 12415 AN: 152030 Hom.: 592 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: 0.0418

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.0600

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0550

Gnomad OTH AF: 0.0876

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

GnomAD4 genome AF: 0.0818 AC: 12439 AN: 152148 Hom.: 598 Cov.: 32 AF XY: 0.0818 AC XY: 6084 AN XY: 74372

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.0747

Gnomad4 ASJ AF: 0.0585

Gnomad4 EAS AF: 0.0417

Gnomad4 SAS AF: 0.0455

Gnomad4 FIN AF: 0.0600

Gnomad4 NFE AF: 0.0550

Gnomad4 OTH AF: 0.0867

Alfa AF: 0.0705 Hom.: 81

Bravo AF: 0.0872

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.66
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11961171; hg19: chr6-11276028;