rs7089209

Variant names:

• chr10-53831553-G-A
• rs7089209
• NM_033056.4:c.3984-20C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-53831553-G-A
• chr10-53831553-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033056.4(PCDH15):​c.3984-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,521,810 control chromosomes in the GnomAD database, including 134,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11786 hom., cov: 33)
  • Exomes 𝑓: 0.42 (122971 hom.)
• Consequence: PCDH15 NM_033056.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0570
• Publications: 10 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-53831553-G-A is Benign according to our data. Variant chr10-53831553-G-A is described in ClinVar as Benign. ClinVar VariationId is 46476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH15	NM_033056.4	c.3984-20C>T		intron_variant	Intron 29 of 32	ENST00000320301.11	NP_149045.3
PCDH15	NM_001384140.1	c.3984-20C>T		intron_variant	Intron 29 of 37	ENST00000644397.2	NP_001371069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11	c.3984-20C>T		intron_variant	Intron 29 of 32	1	NM_033056.4	ENSP00000322604.6
PCDH15	ENST00000644397.2	c.3984-20C>T		intron_variant	Intron 29 of 37		NM_001384140.1	ENSP00000495195.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58115 AN: 151836 Hom.: 11788 Cov.: 33

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.375

GnomAD2 exomes AF: 0.430 AC: 105821 AN: 246134 AF XY: 0.427

Gnomad AFR exome AF: 0.292

Gnomad AMR exome AF: 0.478

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.750

Gnomad FIN exome AF: 0.375

Gnomad NFE exome AF: 0.393

Gnomad OTH exome AF: 0.393

GnomAD4 exome AF: 0.417 AC: 570689 AN: 1369856 Hom.: 122971 Cov.: 21 AF XY: 0.417 AC XY: 286528 AN XY: 686630

African (AFR) AF: 0.295 AC: 9270 AN: 31472

American (AMR) AF: 0.467 AC: 20647 AN: 44190

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 8571 AN: 25502

East Asian (EAS) AF: 0.790 AC: 30878 AN: 39096

South Asian (SAS) AF: 0.471 AC: 39475 AN: 83822

European-Finnish (FIN) AF: 0.386 AC: 20508 AN: 53154

Middle Eastern (MID) AF: 0.308 AC: 1683 AN: 5472

European-Non Finnish (NFE) AF: 0.404 AC: 416392 AN: 1029882

Other (OTH) AF: 0.406 AC: 23265 AN: 57266

GnomAD4 genome AF: 0.383 AC: 58131 AN: 151954 Hom.: 11786 Cov.: 33 AF XY: 0.384 AC XY: 28486 AN XY: 74272

African (AFR) AF: 0.301 AC: 12457 AN: 41440

American (AMR) AF: 0.407 AC: 6206 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1198 AN: 3458

East Asian (EAS) AF: 0.748 AC: 3867 AN: 5168

South Asian (SAS) AF: 0.481 AC: 2316 AN: 4816

European-Finnish (FIN) AF: 0.373 AC: 3932 AN: 10542

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.397 AC: 26958 AN: 67958

Other (OTH) AF: 0.377 AC: 797 AN: 2112

Alfa AF: 0.378 Hom.: 2403

Bravo AF: 0.381

Asia WGS AF: 0.566 AC: 1966 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Oct 29, 2010

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 1F Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	13
DANN	Benign	0.45
PhyloP100		-0.057
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: rs7089209; hg19: chr10-55591313; COSMIC: COSV57367938;