rs7067601

chr10-68304213-C-T

Variant summary

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

The NM_022129.4(PBLD):c.84+2548G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,152 control chromosomes in the GnomAD database, including 47,823 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 (47823 hom., cov: 33)
• Consequence: PBLD NM_022129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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=-0.88).
• 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	UniProt
PBLD	NM_022129.4	c.84+2548G>A		intron_variant		ENST00000358769.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBLD	ENST00000358769.7	c.84+2548G>A		intron_variant		5	NM_022129.4	P1

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119751 AN: 152034 Hom.: 47791 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: 0.788 AC: 119839 AN: 152152 Hom.: 47823 Cov.: 33 AF XY: 0.784 AC XY: 58291 AN XY: 74388

Gnomad4 AFR AF: 0.669

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: 0.794 AC: 2759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.3
Dann	Benign	0.83

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: rs7067601; hg19: chr10-70063970;