rs7093302

Variant names:

• chr10-54183424-T-C
• rs7093302
• NM_033056.4:c.1590+20A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-54183424-T-C
• chr10-54183424-T-G

Variant summary

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

The NM_001384140.1(PCDH15):​c.1590+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 1,589,456 control chromosomes in the GnomAD database, including 412,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42942 hom., cov: 34)
  • Exomes 𝑓: 0.71 (369295 hom.)
• Consequence: PCDH15 NM_001384140.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.62
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 10-54183424-T-C is Benign according to our data. Variant chr10-54183424-T-C is described in ClinVar as Benign. ClinVar VariationId is 262145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 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.1590+20A>G		intron	N/A	NP_149045.3
	PCDH15	NM_001384140.1	MANE Select	c.1590+20A>G		intron	N/A	NP_001371069.1	Q96QU1-7
	PCDH15	NM_001142763.2		c.1605+20A>G		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.1590+20A>G		intron	N/A	ENSP00000322604.6	Q96QU1-1
	PCDH15	ENST00000644397.2	MANE Select	c.1590+20A>G		intron	N/A	ENSP00000495195.1	Q96QU1-7
	PCDH15	ENST00000395445.6	TSL:1	c.1611+20A>G		intron	N/A	ENSP00000378832.2	Q96QU1-4

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112319 AN: 151900 Hom.: 42891 Cov.: 34

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.755

GnomAD2 exomes AF: 0.661 AC: 165986 AN: 251122 AF XY: 0.660

Gnomad AFR exome AF: 0.850

Gnomad AMR exome AF: 0.608

Gnomad ASJ exome AF: 0.760

Gnomad EAS exome AF: 0.141

Gnomad FIN exome AF: 0.718

Gnomad NFE exome AF: 0.741

Gnomad OTH exome AF: 0.703

GnomAD4 exome AF: 0.707 AC: 1016282 AN: 1437440 Hom.: 369295 Cov.: 31 AF XY: 0.703 AC XY: 504028 AN XY: 716668

African (AFR) AF: 0.858 AC: 28113 AN: 32764

American (AMR) AF: 0.624 AC: 27846 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 19810 AN: 26010

East Asian (EAS) AF: 0.113 AC: 4453 AN: 39574

South Asian (SAS) AF: 0.559 AC: 47958 AN: 85762

European-Finnish (FIN) AF: 0.714 AC: 37991 AN: 53178

Middle Eastern (MID) AF: 0.741 AC: 4244 AN: 5726

European-Non Finnish (NFE) AF: 0.738 AC: 804297 AN: 1090214

Other (OTH) AF: 0.698 AC: 41570 AN: 59562

GnomAD4 genome AF: 0.740 AC: 112426 AN: 152016 Hom.: 42942 Cov.: 34 AF XY: 0.730 AC XY: 54236 AN XY: 74332

African (AFR) AF: 0.847 AC: 35043 AN: 41382

American (AMR) AF: 0.708 AC: 10817 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2657 AN: 3468

East Asian (EAS) AF: 0.136 AC: 699 AN: 5154

South Asian (SAS) AF: 0.534 AC: 2576 AN: 4820

European-Finnish (FIN) AF: 0.709 AC: 7506 AN: 10586

Middle Eastern (MID) AF: 0.815 AC: 238 AN: 292

European-Non Finnish (NFE) AF: 0.744 AC: 50567 AN: 68008

Other (OTH) AF: 0.751 AC: 1586 AN: 2112

Alfa AF: 0.741 Hom.: 65782

Bravo AF: 0.742

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Autosomal recessive nonsyndromic hearing loss 23 (1)
-	-	1	not specified (1)
-	-	1	Usher syndrome type 1F (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.36
PhyloP100		-2.6
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: rs7093302; hg19: chr10-55943184; COSMIC: COSV57418326;