rs1930165

Variant names:

• chr10-54542170-G-A
• rs1930165
• NM_033056.4:c.92-14293C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-54542170-G-A
• chr10-54542170-G-C
• chr10-54542170-G-T

Variant summary

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

The NM_033056.4(PCDH15):​c.92-14293C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,992 control chromosomes in the GnomAD database, including 15,462 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 0.44 (15462 hom., cov: 33)
• Consequence: PCDH15 NM_033056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419
• Publications: 2 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, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia
• Usher syndrome type 1

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

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

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

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000234173 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH15	NM_033056.4	c.92-14293C>T		intron_variant	Intron 2 of 32	ENST00000320301.11	NP_149045.3
PCDH15	NM_001384140.1	c.92-14293C>T		intron_variant	Intron 2 of 37	ENST00000644397.2	NP_001371069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11	c.92-14293C>T		intron_variant	Intron 2 of 32	1	NM_033056.4	ENSP00000322604.6
PCDH15	ENST00000644397.2	c.92-14293C>T		intron_variant	Intron 2 of 37		NM_001384140.1	ENSP00000495195.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67105 AN: 151874 Hom.: 15460 Cov.: 33

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.442 AC: 67145 AN: 151992 Hom.: 15462 Cov.: 33 AF XY: 0.443 AC XY: 32934 AN XY: 74288

African (AFR) AF: 0.369 AC: 15303 AN: 41468

American (AMR) AF: 0.390 AC: 5958 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1594 AN: 3466

East Asian (EAS) AF: 0.747 AC: 3850 AN: 5154

South Asian (SAS) AF: 0.598 AC: 2887 AN: 4826

European-Finnish (FIN) AF: 0.438 AC: 4617 AN: 10552

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.463 AC: 31430 AN: 67942

Other (OTH) AF: 0.430 AC: 905 AN: 2106

Alfa AF: 0.451 Hom.: 26510

Bravo AF: 0.431

Asia WGS AF: 0.614 AC: 2131 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.83
DANN	Benign	0.40
PhyloP100		-0.42
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: rs1930165; hg19: chr10-56301930;