10-68303779-A-G

Variant names:

• chr10-68303779-A-G
• rs4517412
• NM_022129.4:c.84+2982T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022129.4(PBLD):​c.84+2982T>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 151,300 control chromosomes in the GnomAD database, including 47,480 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 (47480 hom., cov: 29)
• Consequence: PBLD NM_022129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• Publications: 1 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=-0.81).
• 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 rank	MANE	Protein	UniProt
PBLD	NM_022129.4	c.84+2982T>C		intron_variant	Intron 2 of 9	ENST00000358769.7	NP_071412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBLD	ENST00000358769.7	c.84+2982T>C		intron_variant	Intron 2 of 9	5	NM_022129.4	ENSP00000351619.2

Frequencies

GnomAD3 genomes AF: 0.787 AC: 118990 AN: 151182 Hom.: 47448 Cov.: 29

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.850

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: 119078 AN: 151300 Hom.: 47480 Cov.: 29 AF XY: 0.783 AC XY: 57837 AN XY: 73876

African (AFR) AF: 0.667 AC: 27493 AN: 41200

American (AMR) AF: 0.776 AC: 11786 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2778 AN: 3460

East Asian (EAS) AF: 0.847 AC: 4353 AN: 5140

South Asian (SAS) AF: 0.749 AC: 3596 AN: 4804

European-Finnish (FIN) AF: 0.788 AC: 8191 AN: 10398

Middle Eastern (MID) AF: 0.856 AC: 250 AN: 292

European-Non Finnish (NFE) AF: 0.858 AC: 58188 AN: 67826

Other (OTH) AF: 0.805 AC: 1686 AN: 2094

Alfa AF: 0.831 Hom.: 34994

Bravo AF: 0.780

Asia WGS AF: 0.792 AC: 2755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.1
DANN	Benign	0.64
PhyloP100		1.8
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: rs4517412; hg19: chr10-70063536;