rs17629216

Positions:

• chr5-141152828-G-A

Variant summary

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

The NM_018939.4(PCDHB6):​c.*186G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 458,712 control chromosomes in the GnomAD database, including 599 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 0.044 (179 hom., cov: 32)
  • Exomes 𝑓: 0.049 (420 hom.)
• Consequence: PCDHB6 NM_018939.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199

Genes affected

PCDHB6 (HGNC:8691): (protocadherin beta 6) This gene is a member of the protocadherin beta gene cluster, one of three related gene clusters tandemly linked on chromosome five. The gene clusters demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. Unlike the alpha and gamma clusters, the transcripts from these genes do not share common 3' exons. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell neural connections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDHB6	NM_018939.4	c.*186G>A		3_prime_UTR_variant	1/1	ENST00000231136.4
PCDHB6	NM_001303145.2	c.*186G>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDHB6	ENST00000231136.4	c.*186G>A		3_prime_UTR_variant	1/1		NM_018939.4	P1
	ENST00000624192.1	n.73-15645C>T		intron_variant, non_coding_transcript_variant		5
	ENST00000624802.1	n.364+19605C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0445 AC: 6733 AN: 151466 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.0370

Gnomad ASJ AF: 0.0557

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0173

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.0414

GnomAD4 exome AF: 0.0495 AC: 15193 AN: 307130 Hom.: 420 Cov.: 5 AF XY: 0.0501 AC XY: 7750 AN XY: 154614

Gnomad4 AFR exome AF: 0.0270

Gnomad4 AMR exome AF: 0.0322

Gnomad4 ASJ exome AF: 0.0527

Gnomad4 EAS exome AF: 0.0000905

Gnomad4 SAS exome AF: 0.0155

Gnomad4 FIN exome AF: 0.0567

Gnomad4 NFE exome AF: 0.0566

Gnomad4 OTH exome AF: 0.0430

GnomAD4 genome AF: 0.0444 AC: 6734 AN: 151582 Hom.: 179 Cov.: 32 AF XY: 0.0432 AC XY: 3200 AN XY: 74012

Gnomad4 AFR AF: 0.0283

Gnomad4 AMR AF: 0.0368

Gnomad4 ASJ AF: 0.0557

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.0179

Gnomad4 FIN AF: 0.0573

Gnomad4 NFE AF: 0.0583

Gnomad4 OTH AF: 0.0410

Alfa AF: 0.0513 Hom.: 269

Bravo AF: 0.0415

Asia WGS AF: 0.00924 AC: 33 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.4
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: rs17629216; hg19: chr5-140532409;