rs6885387

Positions:

• chr5-26939070-G-A

Variant summary

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

The ENST00000231021.9(CDH9):​c.229-23146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 151,612 control chromosomes in the GnomAD database, including 25,094 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 0.57 (25094 hom., cov: 32)
• Consequence: CDH9 ENST00000231021.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485

Genes affected

CDH9 (HGNC:1768): (cadherin 9) This gene encodes a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. The extracellular domain consists of 5 subdomains, each containing a cadherin motif, and appears to determine the specificity of the protein's homophilic cell adhesion activity. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH9	NM_016279.4	c.229-23146C>T		intron_variant		ENST00000231021.9	NP_057363.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH9	ENST00000231021.9	c.229-23146C>T		intron_variant		1	NM_016279.4	ENSP00000231021	P1
CDH9	ENST00000505045.1	n.402-23146C>T		intron_variant, non_coding_transcript_variant		1
CDH9	ENST00000511822.1	c.229-23146C>T		intron_variant		4		ENSP00000422538
CDH9	ENST00000513289.5	c.229-23146C>T		intron_variant		3		ENSP00000426239

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86503 AN: 151494 Hom.: 25069 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.571 AC: 86572 AN: 151612 Hom.: 25094 Cov.: 32 AF XY: 0.565 AC XY: 41859 AN XY: 74044

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.559

Alfa AF: 0.586 Hom.: 24895

Bravo AF: 0.558

Asia WGS AF: 0.351 AC: 1205 AN: 3428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs6885387; hg19: chr5-26939178;