rs1867569

Variant names:

• chr10-68326401-C-T
• rs1867569
• NM_022129.4:c.-60+6383G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 -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 rank	MANE	Protein	UniProt
PBLD	NM_022129.4	c.-60+6383G>A		intron_variant	Intron 1 of 9	ENST00000358769.7	NP_071412.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBLD	ENST00000358769.7	c.-60+6383G>A		intron_variant	Intron 1 of 9	5	NM_022129.4	ENSP00000351619.2
PBLD	ENST00000309049.8	c.-63+6383G>A		intron_variant	Intron 1 of 9	1		ENSP00000308466.4
PBLD	ENST00000495025.2	c.-63+6383G>A		intron_variant	Intron 1 of 8	5		ENSP00000476306.1

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

African (AFR) AF: 0.0886 AC: 3675 AN: 41472

American (AMR) AF: 0.0873 AC: 1334 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3470

East Asian (EAS) AF: 0.194 AC: 1003 AN: 5176

South Asian (SAS) AF: 0.111 AC: 535 AN: 4816

European-Finnish (FIN) AF: 0.0436 AC: 462 AN: 10600

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0267 AC: 1817 AN: 68018

Other (OTH) AF: 0.0426 AC: 90 AN: 2112

Alfa AF: 0.0415 Hom.: 107

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
PhyloP100		1.1
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: rs1867569; hg19: chr10-70086158;