5-31305158-C-T

Variant summary

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

The NM_004932.4(CDH6):c.1000-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 1,597,944 control chromosomes in the GnomAD database, including 3,336 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 0.058 (269 hom., cov: 32)
  • Exomes 𝑓: 0.062 (3067 hom.)
• Consequence: CDH6 NM_004932.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.436

Genes affected

CDH6 (HGNC:1765): (cadherin 6) This gene encodes a member of the cadherin superfamily. Cadherins are membrane glycoproteins that mediate homophilic cell-cell adhesion and play critical roles in cell differentiation and morphogenesis. The encoded protein is a type II cadherin and may play a role in kidney development as well as endometrium and placenta formation. Decreased expression of this gene may be associated with tumor growth and metastasis. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH6	NM_004932.4	c.1000-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000265071.3
CDH6	NM_001362435.2	c.1000-16C>T		splice_polypyrimidine_tract_variant, intron_variant
CDH6	XM_011513921.4	c.1000-16C>T		splice_polypyrimidine_tract_variant, intron_variant
CDH6	XM_047416591.1	c.1000-16C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH6	ENST00000265071.3	c.1000-16C>T		splice_polypyrimidine_tract_variant, intron_variant		2	NM_004932.4	P1
CDH6	ENST00000514738.5	c.835-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0579 AC: 8799 AN: 152088 Hom.: 270 Cov.: 32

Gnomad AFR AF: 0.0539

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0420

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.0503

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0636

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0601

Gnomad OTH AF: 0.0516

GnomAD3 exomes AF: 0.0610 AC: 14706 AN: 241110 Hom.: 534 AF XY: 0.0645 AC XY: 8399 AN XY: 130200

Gnomad AFR exome AF: 0.0542

Gnomad AMR exome AF: 0.0286

Gnomad ASJ exome AF: 0.0459

Gnomad EAS exome AF: 0.0549

Gnomad SAS exome AF: 0.109

Gnomad FIN exome AF: 0.0594

Gnomad NFE exome AF: 0.0623

Gnomad OTH exome AF: 0.0547

GnomAD4 exome AF: 0.0619 AC: 89480 AN: 1445738 Hom.: 3067 Cov.: 32 AF XY: 0.0632 AC XY: 45336 AN XY: 717532

Gnomad4 AFR exome AF: 0.0555

Gnomad4 AMR exome AF: 0.0297

Gnomad4 ASJ exome AF: 0.0463

Gnomad4 EAS exome AF: 0.0440

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0612

Gnomad4 NFE exome AF: 0.0612

Gnomad4 OTH exome AF: 0.0585

GnomAD4 genome AF: 0.0579 AC: 8809 AN: 152206 Hom.: 269 Cov.: 32 AF XY: 0.0593 AC XY: 4416 AN XY: 74422

Gnomad4 AFR AF: 0.0541

Gnomad4 AMR AF: 0.0419

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.0497

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0636

Gnomad4 NFE AF: 0.0601

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0569 Hom.: 394

Bravo AF: 0.0535

Asia WGS AF: 0.0820 AC: 284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.68
Dann	Benign	0.54

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: rs2287581; hg19: chr5-31305265; COSMIC: COSV54064525; COSMIC: COSV54064525;