rs736535

Positions:

• chr10-68284159-G-A

Variant summary

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

The NM_022129.4(PBLD):​c.*18C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,589,032 control chromosomes in the GnomAD database, including 41,628 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 0.25 (5329 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36299 hom.)
• Consequence: PBLD NM_022129.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17

Genes affected

PBLD (HGNC:23301): (phenazine biosynthesis like protein domain containing) Enables identical protein binding activity. Involved in maintenance of gastrointestinal epithelium; negative regulation of SMAD protein signal transduction; and negative regulation of transforming growth factor beta receptor signaling pathway. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBLD	NM_022129.4	c.*18C>T		3_prime_UTR_variant	10/10	ENST00000358769.7
PBLD	XM_005270028.5	c.*18C>T		3_prime_UTR_variant	10/10
PBLD	XM_011540060.4	c.*38C>T		3_prime_UTR_variant	10/10
PBLD	XM_017016513.2	c.*38C>T		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBLD	ENST00000358769.7	c.*18C>T		3_prime_UTR_variant	10/10	5	NM_022129.4	P1
PBLD	ENST00000309049.8	c.*18C>T		3_prime_UTR_variant	10/10	1		P1
PBLD	ENST00000336578.5	c.*18C>T		3_prime_UTR_variant	8/8	1
PBLD	ENST00000468798.5	c.213-869C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38429 AN: 151880 Hom.: 5320 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.230

GnomAD3 exomes AF: 0.274 AC: 66975 AN: 244402 Hom.: 10534 AF XY: 0.267 AC XY: 35307 AN XY: 132298

Gnomad AFR exome AF: 0.315

Gnomad AMR exome AF: 0.458

Gnomad ASJ exome AF: 0.240

Gnomad EAS exome AF: 0.336

Gnomad SAS exome AF: 0.336

Gnomad FIN exome AF: 0.271

Gnomad NFE exome AF: 0.191

Gnomad OTH exome AF: 0.246

GnomAD4 exome AF: 0.216 AC: 309861 AN: 1437034 Hom.: 36299 Cov.: 27 AF XY: 0.217 AC XY: 155637 AN XY: 716070

Gnomad4 AFR exome AF: 0.312

Gnomad4 AMR exome AF: 0.437

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.332

Gnomad4 FIN exome AF: 0.268

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.219

GnomAD4 genome AF: 0.253 AC: 38461 AN: 151998 Hom.: 5329 Cov.: 32 AF XY: 0.261 AC XY: 19417 AN XY: 74278

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.229

Alfa AF: 0.206 Hom.: 4632

Bravo AF: 0.263

Asia WGS AF: 0.285 AC: 991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.018
DANN	Benign	0.59

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: rs736535; hg19: chr10-70043916; COSMIC: COSV53266057; COSMIC: COSV53266057;