chr6-11198581-G-A

Variant names:

• chr6-11198581-G-A
• rs11759513
• ENST00000379433.5:c.*2400C>T

Variant summary

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

The NM_182966.4(NEDD9):​c.*2400C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,106 control chromosomes in the GnomAD database, including 6,717 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 0.27 (6716 hom., cov: 32)
  • Exomes 𝑓: 0.28 (1 hom.)
• Consequence: NEDD9 NM_182966.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400
• Publications: 3 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]

ENSG00000247925 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182966.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD9	NM_006403.4	MANE Select	c.460-4889C>T		intron	N/A	NP_006394.1	Q14511-1
	NEDD9	NM_182966.4		c.*2400C>T		3_prime_UTR	Exon 3 of 3	NP_892011.2	Q14511-2
	NEDD9	NM_001142393.2		c.460-4889C>T		intron	N/A	NP_001135865.1	Q14511-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD9	ENST00000379433.5	TSL:1	c.*2400C>T		3_prime_UTR	Exon 3 of 3	ENSP00000368745.5	Q14511-2
	NEDD9	ENST00000379446.10	TSL:1 MANE Select	c.460-4889C>T		intron	N/A	ENSP00000368759.5	Q14511-1
	NEDD9	ENST00000448183.6	TSL:1	n.*572+1690C>T		intron	N/A	ENSP00000395237.2	D6RDV1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40847 AN: 151956 Hom.: 6719 Cov.: 32

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.281 AC: 9 AN: 32 Hom.: 1 Cov.: 0 AF XY: 0.350 AC XY: 7 AN XY: 20

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.200 AC: 4 AN: 20

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.269 AC: 40842 AN: 152074 Hom.: 6716 Cov.: 32 AF XY: 0.278 AC XY: 20642 AN XY: 74334

African (AFR) AF: 0.0838 AC: 3476 AN: 41504

American (AMR) AF: 0.378 AC: 5767 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1065 AN: 3464

East Asian (EAS) AF: 0.510 AC: 2640 AN: 5172

South Asian (SAS) AF: 0.528 AC: 2543 AN: 4818

European-Finnish (FIN) AF: 0.344 AC: 3624 AN: 10550

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20866 AN: 67980

Other (OTH) AF: 0.295 AC: 623 AN: 2114

Alfa AF: 0.274 Hom.: 2781

Bravo AF: 0.259

Asia WGS AF: 0.471 AC: 1638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.41
DANN	Benign	0.39
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11759513; hg19: chr6-11198814;