rs16913796

Variant names:

• chr10-53900064-C-T
• rs16913796
• NM_033056.4:c.3501+3179G>A

Variant summary

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

The NM_001384140.1(PCDH15):​c.3501+3179G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 152,142 control chromosomes in the GnomAD database, including 734 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 0.094 (734 hom., cov: 32)
• Consequence: PCDH15 NM_001384140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662

Genes affected

PCDH15 (HGNC:14674): (protocadherin related 15) This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. It plays an essential role in maintenance of normal retinal and cochlear function. Mutations in this gene result in hearing loss and Usher Syndrome Type IF (USH1F). Extensive alternative splicing resulting in multiple isoforms has been observed in the mouse ortholog. Similar alternatively spliced transcripts are inferred to occur in human, and additional variants are likely to occur. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH15	NM_033056.4	c.3501+3179G>A		intron_variant	Intron 26 of 32	ENST00000320301.11	NP_149045.3
PCDH15	NM_001384140.1	c.3501+3179G>A		intron_variant	Intron 26 of 37	ENST00000644397.2	NP_001371069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11	c.3501+3179G>A		intron_variant	Intron 26 of 32	1	NM_033056.4	ENSP00000322604.6
PCDH15	ENST00000644397.2	c.3501+3179G>A		intron_variant	Intron 26 of 37		NM_001384140.1	ENSP00000495195.1

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14259 AN: 152024 Hom.: 734 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0706

Gnomad ASJ AF: 0.0988

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0915

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0785

Gnomad OTH AF: 0.0840

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

GnomAD4 genome AF: 0.0937 AC: 14255 AN: 152142 Hom.: 734 Cov.: 32 AF XY: 0.0935 AC XY: 6957 AN XY: 74378

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0703

Gnomad4 ASJ AF: 0.0988

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.0917

Gnomad4 FIN AF: 0.0706

Gnomad4 NFE AF: 0.0785

Gnomad4 OTH AF: 0.0827

Alfa AF: 0.0794 Hom.: 678

Bravo AF: 0.0932

Asia WGS AF: 0.0970 AC: 337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.81

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: rs16913796; hg19: chr10-55659824;