20-50748675-C-T

Variant names:

• chr20-50748675-C-T
• rs6512670
• NM_032521.3:c.290-984C>T

Variant summary

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

The NM_032521.3(PARD6B):​c.290-984C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 151,880 control chromosomes in the GnomAD database, including 10,013 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 0.35 (10013 hom., cov: 31)
• Consequence: PARD6B NM_032521.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.876
• Publications: 2 publications found

Genes affected

PARD6B (HGNC:16245): (par-6 family cell polarity regulator beta) This gene is a member of the PAR6 family and encodes a protein with a PSD95/Discs-large/ZO1 (PDZ) domain, an OPR domain and a semi-Cdc42/Rac interactive binding (CRIB) domain. This cytoplasmic protein is involved in asymmetrical cell division and cell polarization processes as a member of a multi-protein complex. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARD6B	NM_032521.3	c.290-984C>T		intron_variant	Intron 2 of 2	ENST00000371610.7	NP_115910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARD6B	ENST00000371610.7	c.290-984C>T		intron_variant	Intron 2 of 2	1	NM_032521.3	ENSP00000360672.2
PARD6B	ENST00000396039.1	c.290-8010C>T		intron_variant	Intron 2 of 2	1		ENSP00000379354.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53357 AN: 151762 Hom.: 10012 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.352 AC: 53387 AN: 151880 Hom.: 10013 Cov.: 31 AF XY: 0.357 AC XY: 26471 AN XY: 74230

African (AFR) AF: 0.273 AC: 11282 AN: 41394

American (AMR) AF: 0.444 AC: 6775 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1448 AN: 3470

East Asian (EAS) AF: 0.638 AC: 3289 AN: 5156

South Asian (SAS) AF: 0.498 AC: 2391 AN: 4802

European-Finnish (FIN) AF: 0.302 AC: 3188 AN: 10542

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.348 AC: 23648 AN: 67934

Other (OTH) AF: 0.393 AC: 826 AN: 2104

Alfa AF: 0.350 Hom.: 1240

Bravo AF: 0.358

Asia WGS AF: 0.512 AC: 1782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.52
PhyloP100		-0.88
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: rs6512670; hg19: chr20-49365212;