rs967473

Variant names:

• chr6-11329190-G-A
• rs967473
• ENST00000448183.6:n.-152-23035C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000448183.6(NEDD9):​n.-152-23035C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,208 control chromosomes in the GnomAD database, including 1,724 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 0.14 (1724 hom., cov: 33)
• Consequence: NEDD9 ENST00000448183.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 7 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]

LOC105374925 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105374925	XR_007059445.1	n.13620G>A		non_coding_transcript_exon_variant	Exon 4 of 4
LOC105374925	XR_007059446.1	n.13249G>A		non_coding_transcript_exon_variant	Exon 7 of 7
LOC105374925	XR_007059447.1	n.11966G>A		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEDD9	ENST00000448183.6	n.-152-23035C>T		intron_variant	Intron 1 of 9	1		ENSP00000395237.2
NEDD9	ENST00000504387.5	c.-152-23035C>T		intron_variant	Intron 1 of 7	2		ENSP00000422871.1
NEDD9	ENST00000397378.7	c.-153+5311C>T		intron_variant	Intron 2 of 3	3		ENSP00000380534.3

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21663 AN: 152090 Hom.: 1714 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0715

Gnomad SAS AF: 0.0674

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.143 AC: 21694 AN: 152208 Hom.: 1724 Cov.: 33 AF XY: 0.145 AC XY: 10781 AN XY: 74408

African (AFR) AF: 0.124 AC: 5155 AN: 41528

American (AMR) AF: 0.248 AC: 3796 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 366 AN: 3472

East Asian (EAS) AF: 0.0713 AC: 369 AN: 5174

South Asian (SAS) AF: 0.0677 AC: 326 AN: 4818

European-Finnish (FIN) AF: 0.184 AC: 1949 AN: 10592

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9352 AN: 68006

Other (OTH) AF: 0.147 AC: 310 AN: 2116

Alfa AF: 0.143 Hom.: 3556

Bravo AF: 0.151

Asia WGS AF: 0.0860 AC: 300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Benign	0.68
PhyloP100		1.4
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: rs967473; hg19: chr6-11329423;