10-68304752-A-G

Position:

• chr10-68304752-A-G

Variant summary

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

The NM_022129.4(PBLD):​c.84+2009T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,162 control chromosomes in the GnomAD database, including 47,813 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 0.79 (47813 hom., cov: 33)
• Consequence: PBLD NM_022129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.694

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]

PBLD (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PBLD	NM_022129.4	c.84+2009T>C		intron_variant		ENST00000358769.7	NP_071412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PBLD	ENST00000358769.7	c.84+2009T>C		intron_variant		5	NM_022129.4	ENSP00000351619.2

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119726 AN: 152044 Hom.: 47781 Cov.: 33

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.804

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

GnomAD4 genome AF: 0.787 AC: 119814 AN: 152162 Hom.: 47813 Cov.: 33 AF XY: 0.783 AC XY: 58278 AN XY: 74392

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.790

Gnomad4 NFE AF: 0.858

Gnomad4 OTH AF: 0.806

Alfa AF: 0.830 Hom.: 23995

Bravo AF: 0.780

Asia WGS AF: 0.793 AC: 2757 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.3
DANN	Benign	0.63

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: rs10733843; hg19: chr10-70064509;