rs4675502

Positions:

• chr2-205221447-G-A
• chr2-205221447-G-C

Variant summary

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

The NM_001302769.2(PARD3B):​c.2141-24331G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 151,990 control chromosomes in the GnomAD database, including 24,320 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 0.56 (24320 hom., cov: 31)
• Consequence: PARD3B NM_001302769.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

Genes affected

PARD3B (HGNC:14446): (par-3 family cell polarity regulator beta) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in several processes, including establishment of cell polarity; establishment of centrosome localization; and establishment or maintenance of epithelial cell apical/basal polarity. Located in cell junction. Part of protein-containing complex. [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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD3B	NM_001302769.2	c.2141-24331G>A		intron_variant		ENST00000406610.7	NP_001289698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD3B	ENST00000406610.7	c.2141-24331G>A		intron_variant		1	NM_001302769.2	ENSP00000385848	P1
PARD3B	ENST00000349953.7	c.2141-24331G>A		intron_variant		1		ENSP00000340280
PARD3B	ENST00000351153.5	c.2141-24331G>A		intron_variant		1		ENSP00000317261
PARD3B	ENST00000358768.6	c.1955-24331G>A		intron_variant		1		ENSP00000351618

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85516 AN: 151872 Hom.: 24300 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.563 AC: 85579 AN: 151990 Hom.: 24320 Cov.: 31 AF XY: 0.567 AC XY: 42131 AN XY: 74276

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.555

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.550

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.532

Alfa AF: 0.461 Hom.: 1744

Bravo AF: 0.566

Asia WGS AF: 0.601 AC: 2094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.65

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: rs4675502; hg19: chr2-206086171;