chr6-11270404-A-G

Variant names:

• chr6-11270404-A-G
• rs4713332
• ENST00000448183.6:n.106+34662T>C

Variant summary

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

The ENST00000448183.6(NEDD9):​n.106+34662T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0531 in 148,942 control chromosomes in the GnomAD database, including 212 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 0.053 (212 hom., cov: 30)
• Consequence: NEDD9 ENST00000448183.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.988
• Publications: 4 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0549 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+35588T>C		intron	N/A	NP_001135865.1
	NEDD9	NR_073131.1		n.468+34662T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD9	ENST00000448183.6	TSL:1	n.106+34662T>C		intron	N/A	ENSP00000395237.2
	NEDD9	ENST00000504387.5	TSL:2	c.12+35588T>C		intron	N/A	ENSP00000422871.1
	NEDD9	ENST00000397378.7	TSL:3	c.12+35588T>C		intron	N/A	ENSP00000380534.3

Frequencies

GnomAD3 genomes AF: 0.0531 AC: 7908 AN: 148842 Hom.: 211 Cov.: 30

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0586

Gnomad EAS AF: 0.0386

Gnomad SAS AF: 0.0436

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.0546

Gnomad OTH AF: 0.0616

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

GnomAD4 genome AF: 0.0531 AC: 7912 AN: 148942 Hom.: 212 Cov.: 30 AF XY: 0.0540 AC XY: 3913 AN XY: 72412

African (AFR) AF: 0.0496 AC: 2002 AN: 40384

American (AMR) AF: 0.0581 AC: 869 AN: 14958

Ashkenazi Jewish (ASJ) AF: 0.0586 AC: 203 AN: 3464

East Asian (EAS) AF: 0.0385 AC: 197 AN: 5118

South Asian (SAS) AF: 0.0437 AC: 206 AN: 4714

European-Finnish (FIN) AF: 0.0597 AC: 572 AN: 9584

Middle Eastern (MID) AF: 0.138 AC: 40 AN: 290

European-Non Finnish (NFE) AF: 0.0546 AC: 3684 AN: 67458

Other (OTH) AF: 0.0610 AC: 126 AN: 2066

Alfa AF: 0.0556 Hom.: 327

Bravo AF: 0.0546

Asia WGS AF: 0.0480 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.32
PhyloP100		0.99
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: rs4713332; hg19: chr6-11270637;