chr10-54651449-G-A

Variant names:

• chr10-54651449-G-A
• rs1336190
• NM_033056.4:c.91+12723C>T

Variant summary

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

The NM_001384140.1(PCDH15):​c.91+12723C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,972 control chromosomes in the GnomAD database, including 12,620 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 0.39 (12620 hom., cov: 32)
• Consequence: PCDH15 NM_001384140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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]

ENSG00000234173 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH15	NM_033056.4	c.91+12723C>T		intron_variant	Intron 2 of 32	ENST00000320301.11	NP_149045.3
PCDH15	NM_001384140.1	c.91+12723C>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.91+12723C>T		intron_variant	Intron 2 of 32	1	NM_033056.4	ENSP00000322604.6
PCDH15	ENST00000644397.2	c.91+12723C>T		intron_variant	Intron 2 of 37		NM_001384140.1	ENSP00000495195.1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58859 AN: 151852 Hom.: 12594 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.388 AC: 58941 AN: 151972 Hom.: 12620 Cov.: 32 AF XY: 0.383 AC XY: 28420 AN XY: 74282

African (AFR) AF: 0.583 AC: 24141 AN: 41408

American (AMR) AF: 0.324 AC: 4944 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1444 AN: 3470

East Asian (EAS) AF: 0.226 AC: 1164 AN: 5152

South Asian (SAS) AF: 0.319 AC: 1541 AN: 4824

European-Finnish (FIN) AF: 0.249 AC: 2641 AN: 10586

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21847 AN: 67956

Other (OTH) AF: 0.398 AC: 839 AN: 2110

Alfa AF: 0.352 Hom.: 4248

Bravo AF: 0.408

Asia WGS AF: 0.300 AC: 1046 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.72
DANN	Benign	0.67
PhyloP100		-0.30
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

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Other links and lift over

dbSNP: rs1336190; hg19: chr10-56411209;