6-11263851-C-T

Variant names:

• chr6-11263851-C-T
• rs41463745
• ENST00000448183.6:n.106+41215G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000448183.6(NEDD9):​n.106+41215G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0686 in 152,206 control chromosomes in the GnomAD database, including 371 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 (371 hom., cov: 32)
• Consequence: NEDD9 ENST00000448183.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0995 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000448183.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD9	NM_001142393.2		c.12+42141G>A		intron	N/A	NP_001135865.1
	NEDD9	NR_073131.1		n.468+41215G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD9	ENST00000448183.6	TSL:1	n.106+41215G>A		intron	N/A	ENSP00000395237.2
	NEDD9	ENST00000504387.5	TSL:2	c.12+42141G>A		intron	N/A	ENSP00000422871.1
	NEDD9	ENST00000397378.7	TSL:3	c.12+42141G>A		intron	N/A	ENSP00000380534.3

Frequencies

GnomAD3 genomes AF: 0.0686 AC: 10432 AN: 152088 Hom.: 367 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.0448

Gnomad FIN AF: 0.0606

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0546

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0686 AC: 10444 AN: 152206 Hom.: 371 Cov.: 32 AF XY: 0.0693 AC XY: 5155 AN XY: 74424

African (AFR) AF: 0.102 AC: 4239 AN: 41520

American (AMR) AF: 0.0667 AC: 1020 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0582 AC: 202 AN: 3472

East Asian (EAS) AF: 0.0384 AC: 199 AN: 5178

South Asian (SAS) AF: 0.0450 AC: 217 AN: 4822

European-Finnish (FIN) AF: 0.0606 AC: 642 AN: 10598

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0546 AC: 3715 AN: 68002

Other (OTH) AF: 0.0743 AC: 157 AN: 2114

Alfa AF: 0.0615 Hom.: 67

Bravo AF: 0.0719

Asia WGS AF: 0.0560 AC: 193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.45
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs41463745; hg19: chr6-11264084;