rs10942230

Positions:

• chr5-27005087-T-C

Variant summary

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

The NM_016279.4(CDH9):​c.-49-16705A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,940 control chromosomes in the GnomAD database, including 16,251 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 0.45 (16251 hom., cov: 32)
• Consequence: CDH9 NM_016279.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.345

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH9	NM_016279.4	c.-49-16705A>G		intron_variant		ENST00000231021.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH9	ENST00000231021.9	c.-49-16705A>G		intron_variant		1	NM_016279.4	P1
CDH9	ENST00000505045.1	n.125-16705A>G		intron_variant, non_coding_transcript_variant		1
CDH9	ENST00000511822.1	c.-49-16705A>G		intron_variant		4
CDH9	ENST00000513289.5	c.-49-16705A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68514 AN: 151822 Hom.: 16245 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.451 AC: 68547 AN: 151940 Hom.: 16251 Cov.: 32 AF XY: 0.447 AC XY: 33179 AN XY: 74252

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.416

Alfa AF: 0.463 Hom.: 2810

Bravo AF: 0.433

Asia WGS AF: 0.212 AC: 735 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.76

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: rs10942230; hg19: chr5-27005194;