5-31209260-A-G

Position:

• chr5-31209260-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.-129+15374A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 152,150 control chromosomes in the GnomAD database, including 53,231 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 0.83 (53231 hom., cov: 31)
• Consequence: CDH6 NM_004932.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401

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]

ENSG00000254138 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH6	NM_004932.4	c.-129+15374A>G		intron_variant		ENST00000265071.3	NP_004923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH6	ENST00000265071.3	c.-129+15374A>G		intron_variant		2	NM_004932.4	ENSP00000265071.2

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126837 AN: 152032 Hom.: 53191 Cov.: 31

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.834 AC: 126933 AN: 152150 Hom.: 53231 Cov.: 31 AF XY: 0.834 AC XY: 62023 AN XY: 74384

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.857

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.903

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.879

Gnomad4 OTH AF: 0.826

Alfa AF: 0.870 Hom.: 116406

Bravo AF: 0.823

Asia WGS AF: 0.777 AC: 2707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.4
DANN	Benign	0.77

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: rs4535467; hg19: chr5-31209367;