rs12571150

Variant names:

• chr10-54786295-C-T
• rs12571150
• NM_033056.4:c.-29+14630G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384140.1(PCDH15):​c.-29+14630G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,854 control chromosomes in the GnomAD database, including 5,733 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 0.27 (5733 hom., cov: 32)
• Consequence: PCDH15 NM_001384140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 1 publications found

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]

PCDH15 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 23

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• Usher syndrome type 1

  Inheritance: AR, Unknown Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Usher syndrome type 1F

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384140.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH15	NM_033056.4	MANE Plus Clinical	c.-29+14630G>A		intron	N/A	NP_149045.3
	PCDH15	NM_001384140.1	MANE Select	c.-29+14630G>A		intron	N/A	NP_001371069.1	Q96QU1-7
	PCDH15	NM_001142763.2		c.-29+14630G>A		intron	N/A	NP_001136235.1	A2A3D8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH15	ENST00000320301.11	TSL:1 MANE Plus Clinical	c.-29+14630G>A		intron	N/A	ENSP00000322604.6	Q96QU1-1
	PCDH15	ENST00000644397.2	MANE Select	c.-29+14630G>A		intron	N/A	ENSP00000495195.1	Q96QU1-7
	PCDH15	ENST00000395445.6	TSL:1	c.-29+14630G>A		intron	N/A	ENSP00000378832.2	Q96QU1-4

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40271 AN: 151736 Hom.: 5722 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.266 AC: 40320 AN: 151854 Hom.: 5733 Cov.: 32 AF XY: 0.261 AC XY: 19404 AN XY: 74226

African (AFR) AF: 0.375 AC: 15533 AN: 41406

American (AMR) AF: 0.200 AC: 3048 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 732 AN: 3464

East Asian (EAS) AF: 0.168 AC: 865 AN: 5136

South Asian (SAS) AF: 0.208 AC: 1006 AN: 4830

European-Finnish (FIN) AF: 0.208 AC: 2198 AN: 10590

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16131 AN: 67898

Other (OTH) AF: 0.271 AC: 572 AN: 2108

Alfa AF: 0.244 Hom.: 3757

Bravo AF: 0.274

Asia WGS AF: 0.209 AC: 729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.36
PhyloP100		-0.067
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12571150; hg19: chr10-56546055;