rs2008734

Positions:

• chr11-73655652-G-A
• chr11-73655652-G-C

Variant summary

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

The NM_021200.3(PLEKHB1):​c.391-151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 632,112 control chromosomes in the GnomAD database, including 87,847 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 0.48 (18779 hom., cov: 32)
  • Exomes 𝑓: 0.53 (69068 hom.)
• Consequence: PLEKHB1 NM_021200.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831

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=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHB1	NM_021200.3	c.391-151G>A		intron_variant		ENST00000354190.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHB1	ENST00000354190.10	c.391-151G>A		intron_variant		1	NM_021200.3

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73201 AN: 151934 Hom.: 18770 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.493

GnomAD4 exome AF: 0.530 AC: 254533 AN: 480058 Hom.: 69068 AF XY: 0.523 AC XY: 131994 AN XY: 252142

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.554

Gnomad4 ASJ exome AF: 0.534

Gnomad4 EAS exome AF: 0.479

Gnomad4 SAS exome AF: 0.403

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.524

GnomAD4 genome AF: 0.482 AC: 73238 AN: 152054 Hom.: 18779 Cov.: 32 AF XY: 0.482 AC XY: 35797 AN XY: 74312

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.547

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.495

Alfa AF: 0.511 Hom.: 3682

Bravo AF: 0.476

Asia WGS AF: 0.432 AC: 1503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.84

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: rs2008734; hg19: chr11-73366697; COSMIC: COSV57050294; COSMIC: COSV57050294;