rs4437462

Positions:

• chr6-11310186-C-T

Variant summary

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

The ENST00000448183.6(NEDD9):​c.-152-4031G>A variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,164 control chromosomes in the GnomAD database, including 2,145 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 0.16 (2145 hom., cov: 32)
• Consequence: NEDD9 ENST00000448183.6 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105374925	XR_001743967.2	n.7740+4004C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEDD9	ENST00000448183.6	c.-152-4031G>A		intron_variant, NMD_transcript_variant		1		ENSP00000395237
NEDD9	ENST00000397378.7	c.-152-4031G>A		intron_variant		3		ENSP00000380534
NEDD9	ENST00000504387.5	c.-152-4031G>A		intron_variant		2		ENSP00000422871	A1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24749 AN: 152046 Hom.: 2143 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0506

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.163 AC: 24756 AN: 152164 Hom.: 2145 Cov.: 32 AF XY: 0.161 AC XY: 12014 AN XY: 74404

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0503

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.161

Alfa AF: 0.146 Hom.: 1944

Bravo AF: 0.164

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4437462; hg19: chr6-11310419;