rs9527676

Positions:

• chr13-57641142-G-A
• chr13-57641142-G-C
• chr13-57641142-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040429.3(PCDH17):​c.2565+6031G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,518 control chromosomes in the GnomAD database, including 28,292 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 0.60 (28292 hom., cov: 30)
• Consequence: PCDH17 NM_001040429.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

Genes affected

PCDH17 (HGNC:14267): (protocadherin 17) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein contains six extracellular cadherin domains, a transmembrane domain, and a cytoplasmic tail differing from those of the classical cadherins. The encoded protein may play a role in the establishment and function of specific cell-cell connections in the brain. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH17	NM_001040429.3	c.2565+6031G>A		intron_variant		ENST00000377918.8	NP_001035519.1
PCDH17	XM_005266357.3	c.2565+6031G>A		intron_variant			XP_005266414.1
PCDH17	XM_047430276.1	c.2565+6031G>A		intron_variant			XP_047286232.1
PCDH17	XM_017020547.2	c.2565+6031G>A		intron_variant			XP_016876036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH17	ENST00000377918.8	c.2565+6031G>A		intron_variant		1	NM_001040429.3	ENSP00000367151.3
PCDH17	ENST00000484979.5	n.2565+6031G>A		intron_variant		1		ENSP00000432899.1
PCDH17	ENST00000612954.4	c.729+6031G>A		intron_variant		5		ENSP00000481329.1
PCDH17	ENST00000615375.1	c.99+6031G>A		intron_variant		4		ENSP00000483215.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91330 AN: 151402 Hom.: 28262 Cov.: 30

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.603 AC: 91415 AN: 151518 Hom.: 28292 Cov.: 30 AF XY: 0.607 AC XY: 44957 AN XY: 74048

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.665

Alfa AF: 0.559 Hom.: 3344

Bravo AF: 0.598

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	7.0
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs9527676; hg19: chr13-58215276; COSMIC: COSV64978391;