rs4675490

Positions:

• chr2-205077837-A-G
• chr2-205077837-A-T

Variant summary

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

The ENST00000406610.7(PARD3B):​c.505-26589A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,944 control chromosomes in the GnomAD database, including 13,105 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 0.41 (13105 hom., cov: 31)
• Consequence: PARD3B ENST00000406610.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.931

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PARD3B	NM_001302769.2	c.505-26589A>G		intron_variant		ENST00000406610.7	NP_001289698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PARD3B	ENST00000406610.7	c.505-26589A>G		intron_variant		1	NM_001302769.2	ENSP00000385848	P1
PARD3B	ENST00000349953.7	c.505-26589A>G		intron_variant		1		ENSP00000340280
PARD3B	ENST00000351153.5	c.505-26589A>G		intron_variant		1		ENSP00000317261
PARD3B	ENST00000358768.6	c.505-26589A>G		intron_variant		1		ENSP00000351618

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62160 AN: 151828 Hom.: 13091 Cov.: 31

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.409 AC: 62215 AN: 151944 Hom.: 13105 Cov.: 31 AF XY: 0.413 AC XY: 30641 AN XY: 74262

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.385

Alfa AF: 0.411 Hom.: 27001

Bravo AF: 0.416

Asia WGS AF: 0.500 AC: 1735 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	10
DANN	Benign	0.71

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: rs4675490; hg19: chr2-205942560;