10-68309040-C-T

Variant names:

• chr10-68309040-C-T
• rs10762217
• NM_022129.4:c.-59-2137G>A

Variant summary

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

The NM_022129.4(PBLD):​c.-59-2137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 149,670 control chromosomes in the GnomAD database, including 46,852 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 0.78 (46852 hom., cov: 31)
• Consequence: PBLD NM_022129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBLD	NM_022129.4	c.-59-2137G>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.-59-2137G>A		intron_variant	Intron 1 of 9	5	NM_022129.4	ENSP00000351619.2
PBLD	ENST00000309049.8	c.-62-2134G>A		intron_variant	Intron 1 of 9	1		ENSP00000308466.4
PBLD	ENST00000495025.2	c.-62-2134G>A		intron_variant	Intron 1 of 8	5		ENSP00000476306.1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 116028 AN: 149552 Hom.: 46820 Cov.: 31

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.797

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

GnomAD4 genome AF: 0.776 AC: 116113 AN: 149670 Hom.: 46852 Cov.: 31 AF XY: 0.771 AC XY: 56222 AN XY: 72888

African (AFR) AF: 0.648 AC: 26317 AN: 40614

American (AMR) AF: 0.753 AC: 11071 AN: 14700

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2785 AN: 3468

East Asian (EAS) AF: 0.813 AC: 3898 AN: 4796

South Asian (SAS) AF: 0.727 AC: 3419 AN: 4700

European-Finnish (FIN) AF: 0.780 AC: 8116 AN: 10404

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.854 AC: 57832 AN: 67702

Other (OTH) AF: 0.798 AC: 1662 AN: 2082

Alfa AF: 0.819 Hom.: 20819

Bravo AF: 0.765

Asia WGS AF: 0.770 AC: 2633 AN: 3420

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.27
PhyloP100		-0.18
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: rs10762217; hg19: chr10-70068797;