rs591804

chr11-73652165-G-A

Variant summary

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

The NM_021200.3(PLEKHB1):c.350+275G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 465,786 control chromosomes in the GnomAD database, including 99,746 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 0.63 (30408 hom., cov: 31)
  • Exomes 𝑓: 0.66 (69338 hom.)
• Consequence: PLEKHB1 NM_021200.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392

Genes affected

PLEKHB1 (HGNC:19079): (pleckstrin homology domain containing B1) Predicted to enable protein C-terminus binding activity and protein homodimerization activity. Predicted to be involved in regulation of cell differentiation. Is integral component of membrane. [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 (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHB1	NM_021200.3	c.350+275G>A		intron_variant		ENST00000354190.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHB1	ENST00000354190.10	c.350+275G>A		intron_variant		1	NM_021200.3

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95580 AN: 151892 Hom.: 30404 Cov.: 31

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.612

GnomAD4 exome AF: 0.663 AC: 208030 AN: 313776 Hom.: 69338 AF XY: 0.660 AC XY: 108956 AN XY: 164976

Gnomad4 AFR exome AF: 0.533

Gnomad4 AMR exome AF: 0.649

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.681

Gnomad4 SAS exome AF: 0.636

Gnomad4 FIN exome AF: 0.688

Gnomad4 NFE exome AF: 0.672

Gnomad4 OTH exome AF: 0.655

GnomAD4 genome AF: 0.629 AC: 95623 AN: 152010 Hom.: 30408 Cov.: 31 AF XY: 0.630 AC XY: 46829 AN XY: 74296

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.612

Alfa AF: 0.657 Hom.: 8153

Bravo AF: 0.619

Asia WGS AF: 0.646 AC: 2245 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	1.2
Dann	Benign	0.36

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: rs591804; hg19: chr11-73363210;