rs2910326

Variant names:

• chr5-141208801-C-T
• rs2910326
• NM_018932.4:c.-107C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

PCDHB@ (HGNC:8679):

ENSG00000280029 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PCDHB12	NM_018932.4	c.-107C>T		5_prime_UTR_variant	Exon 1 of 1	ENST00000239450.4	NP_061755.1
PCDHB@		n.141208801C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDHB12	ENST00000239450.4	c.-107C>T		5_prime_UTR_variant	Exon 1 of 1	6	NM_018932.4	ENSP00000239450.2

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

African (AFR) AF: 0.673 AC: 13426 AN: 19936

American (AMR) AF: 0.308 AC: 6404 AN: 20798

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 6069 AN: 16036

East Asian (EAS) AF: 0.150 AC: 5169 AN: 34458

South Asian (SAS) AF: 0.296 AC: 13899 AN: 46916

European-Finnish (FIN) AF: 0.319 AC: 15202 AN: 47648

Middle Eastern (MID) AF: 0.440 AC: 1177 AN: 2672

European-Non Finnish (NFE) AF: 0.356 AC: 215289 AN: 605248

Other (OTH) AF: 0.366 AC: 13948 AN: 38146

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

African (AFR) AF: 0.671 AC: 27813 AN: 41474

American (AMR) AF: 0.360 AC: 5503 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1247 AN: 3472

East Asian (EAS) AF: 0.131 AC: 679 AN: 5166

South Asian (SAS) AF: 0.295 AC: 1425 AN: 4826

European-Finnish (FIN) AF: 0.331 AC: 3491 AN: 10544

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23804 AN: 67978

Other (OTH) AF: 0.414 AC: 876 AN: 2114

Alfa AF: 0.381 Hom.: 12250

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
PhyloP100		0.060
PromoterAI		-0.0091	Neutral
Mutation Taster		=299/1	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: rs2910326; hg19: chr5-140588373; COSMIC: COSV53394508;