10-54681391-G-T

Position:

• chr10-54681391-G-T

Variant summary

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

The NM_033056.4(PCDH15):​c.-28-17101C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 152,144 control chromosomes in the GnomAD database, including 242 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 0.052 (242 hom., cov: 32)
• Consequence: PCDH15 NM_033056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.349

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_001384140.1	c.-28-17101C>A		intron_variant		ENST00000644397.2	NP_001371069.1
PCDH15	NM_033056.4	c.-28-17101C>A		intron_variant		ENST00000320301.11	NP_149045.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11	c.-28-17101C>A		intron_variant		1	NM_033056.4	ENSP00000322604
PCDH15	ENST00000644397.2	c.-28-17101C>A		intron_variant			NM_001384140.1	ENSP00000495195

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7862 AN: 152026 Hom.: 243 Cov.: 32

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0449

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0612

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0689

Gnomad OTH AF: 0.0497

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

GnomAD4 genome AF: 0.0516 AC: 7855 AN: 152144 Hom.: 242 Cov.: 32 AF XY: 0.0507 AC XY: 3773 AN XY: 74398

Gnomad4 AFR AF: 0.0166

Gnomad4 AMR AF: 0.0415

Gnomad4 ASJ AF: 0.0449

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0612

Gnomad4 FIN AF: 0.0648

Gnomad4 NFE AF: 0.0688

Gnomad4 OTH AF: 0.0496

Alfa AF: 0.0589 Hom.: 459

Bravo AF: 0.0479

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.36
DANN	Benign	0.60

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: rs7911634; hg19: chr10-56441151;