rs1867569

chr10-68326401-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_022129.4(PBLD):c.-60+6383G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0589 in 152,146 control chromosomes in the GnomAD database, including 383 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 0.059 (383 hom., cov: 32)
• Consequence: PBLD NM_022129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBLD	NM_022129.4	c.-60+6383G>A		intron_variant		ENST00000358769.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBLD	ENST00000358769.7	c.-60+6383G>A		intron_variant		5	NM_022129.4	P1
PBLD	ENST00000309049.8	c.-63+6383G>A		intron_variant		1		P1
PBLD	ENST00000495025.2	c.-63+6383G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0588 AC: 8936 AN: 152028 Hom.: 378 Cov.: 32

Gnomad AFR AF: 0.0885

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0871

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0436

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0267

Gnomad OTH AF: 0.0392

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0589 AC: 8962 AN: 152146 Hom.: 383 Cov.: 32 AF XY: 0.0629 AC XY: 4676 AN XY: 74382

Gnomad4 AFR AF: 0.0886

Gnomad4 AMR AF: 0.0873

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0436

Gnomad4 NFE AF: 0.0267

Gnomad4 OTH AF: 0.0426

Alfa AF: 0.0421 Hom.: 99

Bravo AF: 0.0645

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
Cadd	Benign	18
Dann	Benign	0.92

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: rs1867569; hg19: chr10-70086158;