rs2910326

Positions:

• chr5-141208801-C-T

Variant summary

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

The NM_018932.4(PCDHB12):​c.-107C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 983,920 control chromosomes in the GnomAD database, including 69,424 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 0.43 (15906 hom., cov: 32)
  • Exomes 𝑓: 0.35 (53518 hom.)
• Consequence: PCDHB12 NM_018932.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600

Genes affected

PCDHB12 (HGNC:8683): (protocadherin beta 12) 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. The beta cluster contains 16 genes and 3 pseudogenes, each encoding 6 extracellular cadherin domains and a cytoplasmic tail that deviates from others in the cadherin superfamily. The extracellular domains interact in a homophilic manner to specify differential cell-cell connections. Unlike the alpha and gamma clusters, the transcripts from these genes are made up of only one large exon, not sharing common 3' exons as expected. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins. Their specific functions are unknown but they most likely play a critical role in the establishment and function of specific cell-cell neural connections. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDHB12	NM_018932.4	c.-107C>T		5_prime_UTR_variant	1/1	ENST00000239450.4	NP_061755.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDHB12	ENST00000239450.4	c.-107C>T		5_prime_UTR_variant	1/1		NM_018932.4	ENSP00000239450	P1
	ENST00000624192.1	n.72+32872G>A		intron_variant, non_coding_transcript_variant		5
PCDHB12	ENST00000622978.1	c.-107C>T		5_prime_UTR_variant	1/2	2		ENSP00000485352
PCDHB12	ENST00000624949.1	c.-240C>T		5_prime_UTR_variant	1/2	2		ENSP00000485303

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65274 AN: 151944 Hom.: 15873 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.418

GnomAD4 exome AF: 0.349 AC: 290583 AN: 831858 Hom.: 53518 Cov.: 11 AF XY: 0.346 AC XY: 145480 AN XY: 420066

Gnomad4 AFR exome AF: 0.673

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.378

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.296

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.356

Gnomad4 OTH exome AF: 0.366

GnomAD4 genome AF: 0.430 AC: 65354 AN: 152062 Hom.: 15906 Cov.: 32 AF XY: 0.424 AC XY: 31479 AN XY: 74322

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.414

Alfa AF: 0.365 Hom.: 7918

Bravo AF: 0.444

Asia WGS AF: 0.230 AC: 802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.9
DANN	Benign	0.73

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: rs2910326; hg19: chr5-140588373; COSMIC: COSV53394508;