chr4-30772461-C-A

Position:

• chr4-30772461-C-A

Variant summary

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

The NM_001173523.2(PCDH7):​c.3174+47865C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,092 control chromosomes in the GnomAD database, including 1,718 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 0.14 (1718 hom., cov: 32)
• Consequence: PCDH7 NM_001173523.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

Genes affected

PCDH7 (HGNC:8659): (protocadherin 7) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The gene encodes a protein with an extracellular domain containing 7 cadherin repeats. The gene product is an integral membrane protein that is thought to function in cell-cell recognition and adhesion. Alternative splicing yields isoforms with unique cytoplasmic tails. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH7	NM_001173523.2	c.3174+47865C>A		intron_variant		ENST00000695919.1	NP_001166994.1
PCDH7	NM_032457.4	c.3174+47865C>A		intron_variant			NP_115833.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH7	ENST00000695919.1	c.3174+47865C>A		intron_variant			NM_001173523.2	ENSP00000512266	A1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21284 AN: 151974 Hom.: 1708 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.140 AC: 21299 AN: 152092 Hom.: 1718 Cov.: 32 AF XY: 0.145 AC XY: 10748 AN XY: 74346

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.125

Alfa AF: 0.142 Hom.: 762

Bravo AF: 0.140

Asia WGS AF: 0.243 AC: 846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10517215; hg19: chr4-30774083;