chr10-53831553-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001384140.1(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_001384140.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0570

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 id is 46476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53831553-G-A is described in Lovd as [Benign].

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 link	c.3984-20C>T		intron_variant	Intron 29 of 32	ENST00000320301.11	NP_149045.3	Q96QU1-1
PCDH15	NM_001384140.1 link	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 link	c.3984-20C>T		intron_variant	Intron 29 of 32	1	NM_033056.4	ENSP00000322604.6		Q96QU1-1
PCDH15	ENST00000644397.2 link	c.3984-20C>T		intron_variant	Intron 29 of 37		NM_001384140.1	ENSP00000495195.1		A0A2R8Y6C0

Frequencies

GnomAD3 genomes

AF:

0.383

AC:

58115

AN:

151836

Hom.:

11788

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.417

AC XY:

286528

AN XY:

686630

show subpopulations

Gnomad4 AFR exome

AF:

0.295

AC:

9270

AN:

31472

Gnomad4 AMR exome

AF:

0.467

AC:

20647

AN:

44190

Gnomad4 ASJ exome

AF:

0.336

AC:

8571

AN:

25502

Gnomad4 EAS exome

AF:

0.790

AC:

30878

AN:

39096

Gnomad4 SAS exome

AF:

0.471

AC:

39475

AN:

83822

Gnomad4 FIN exome

AF:

0.386

AC:

20508

AN:

53154

Gnomad4 NFE exome

AF:

0.404

AC:

416392

AN:

1029882

Gnomad4 Remaining exome

AF:

0.406

AC:

23265

AN:

57266

Heterozygous variant carriers

14904

29808

44712

59616

74520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

12770

25540

38310

51080

63850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.383

AC:

58131

AN:

151954

Hom.:

11786

Cov.:

AF XY:

0.384

AC XY:

28486

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.301

AC:

0.300603

AN:

0.300603

Gnomad4 AMR

AF:

0.407

AC:

0.406684

AN:

0.406684

Gnomad4 ASJ

AF:

0.346

AC:

0.346443

AN:

0.346443

Gnomad4 EAS

AF:

0.748

AC:

0.748259

AN:

0.748259

Gnomad4 SAS

AF:

0.481

AC:

0.480897

AN:

0.480897

Gnomad4 FIN

AF:

0.373

AC:

0.372984

AN:

0.372984

Gnomad4 NFE

AF:

0.397

AC:

0.396686

AN:

0.396686

Gnomad4 OTH

AF:

0.377

AC:

0.377367

AN:

0.377367

Heterozygous variant carriers

1798

3597

5395

7194

8992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

566

1132

1698

2264

2830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

LINK: link

Submissions by phenotype

not specified

Benign:4

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

Significance:Benign

Review Status:no assertion criteria provided

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 29, 2010

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

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

DANN

Benign

0.45

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over