rs867987

Positions:

• chr5-31314542-A-G

Variant summary

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

The NM_004932.4(CDH6):​c.1390+1088A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,670 control chromosomes in the GnomAD database, including 6,552 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 0.26 (6552 hom., cov: 29)
• Consequence: CDH6 NM_004932.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH6	NM_004932.4	c.1390+1088A>G		intron_variant		ENST00000265071.3	NP_004923.1
CDH6	NM_001362435.2	c.1390+1088A>G		intron_variant			NP_001349364.1
CDH6	XM_011513921.4	c.1390+1088A>G		intron_variant			XP_011512223.1
CDH6	XM_047416591.1	c.1390+1088A>G		intron_variant			XP_047272547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH6	ENST00000265071.3	c.1390+1088A>G		intron_variant		2	NM_004932.4	ENSP00000265071.2
CDH6	ENST00000514738.5	c.1225+1088A>G		intron_variant		1		ENSP00000424843.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40124 AN: 151550 Hom.: 6553 Cov.: 29

Gnomad AFR AF: 0.0634

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.265 AC: 40124 AN: 151670 Hom.: 6552 Cov.: 29 AF XY: 0.268 AC XY: 19826 AN XY: 74104

Gnomad4 AFR AF: 0.0632

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.263

Alfa AF: 0.318 Hom.: 1730

Bravo AF: 0.249

Asia WGS AF: 0.242 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.3
DANN	Benign	0.69

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: rs867987; hg19: chr5-31314649;