rs736535

Variant names:

• chr10-68284159-G-A
• rs736535
• NM_022129.4:c.*18C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PBLD	NM_022129.4	c.*18C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000358769.7	NP_071412.2
PBLD	XM_005270028.5	c.*18C>T		3_prime_UTR_variant	Exon 10 of 10		XP_005270085.1
PBLD	XM_011540060.4	c.*38C>T		3_prime_UTR_variant	Exon 10 of 10		XP_011538362.1
PBLD	XM_017016513.2	c.*38C>T		3_prime_UTR_variant	Exon 10 of 10		XP_016872002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBLD	ENST00000358769.7	c.*18C>T		3_prime_UTR_variant	Exon 10 of 10	5	NM_022129.4	ENSP00000351619.2
PBLD	ENST00000309049.8	c.*18C>T		3_prime_UTR_variant	Exon 10 of 10	1		ENSP00000308466.4
PBLD	ENST00000336578.5	c.*18C>T		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000338041.1
PBLD	ENST00000468798.5	c.212-869C>T		intron_variant	Intron 2 of 2	3		ENSP00000476261.1

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

GnomAD2 exomes AF: 0.274 AC: 66975 AN: 244402 AF XY: 0.267

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 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

African (AFR) AF: 0.312 AC: 10219 AN: 32780

American (AMR) AF: 0.437 AC: 18965 AN: 43438

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 6281 AN: 25796

East Asian (EAS) AF: 0.323 AC: 12786 AN: 39558

South Asian (SAS) AF: 0.332 AC: 28216 AN: 84886

European-Finnish (FIN) AF: 0.268 AC: 14274 AN: 53284

Middle Eastern (MID) AF: 0.185 AC: 1055 AN: 5718

European-Non Finnish (NFE) AF: 0.188 AC: 205053 AN: 1092078

Other (OTH) AF: 0.219 AC: 13012 AN: 59496

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

African (AFR) AF: 0.310 AC: 12862 AN: 41434

American (AMR) AF: 0.318 AC: 4851 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3466

East Asian (EAS) AF: 0.330 AC: 1703 AN: 5168

South Asian (SAS) AF: 0.326 AC: 1572 AN: 4822

European-Finnish (FIN) AF: 0.271 AC: 2867 AN: 10560

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12987 AN: 67960

Other (OTH) AF: 0.229 AC: 483 AN: 2110

Alfa AF: 0.215 Hom.: 13482

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
PhyloP100		-3.2
Mutation Taster		=100/0	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: rs736535; hg19: chr10-70043916; COSMIC: COSV53266057; COSMIC: COSV53266057;