rs2008734

Variant names:

• chr11-73655652-G-A
• rs2008734
• NM_021200.3:c.391-151G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLEKHB1	NM_021200.3	c.391-151G>A		intron_variant	Intron 5 of 7	ENST00000354190.10	NP_067023.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHB1	ENST00000354190.10	c.391-151G>A		intron_variant	Intron 5 of 7	1	NM_021200.3	ENSP00000346127.5

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

African (AFR) AF: 0.297 AC: 3999 AN: 13462

American (AMR) AF: 0.554 AC: 12336 AN: 22284

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 7703 AN: 14424

East Asian (EAS) AF: 0.479 AC: 14919 AN: 31170

South Asian (SAS) AF: 0.403 AC: 19791 AN: 49164

European-Finnish (FIN) AF: 0.550 AC: 17294 AN: 31426

Middle Eastern (MID) AF: 0.516 AC: 1795 AN: 3478

European-Non Finnish (NFE) AF: 0.565 AC: 162510 AN: 287572

Other (OTH) AF: 0.524 AC: 14186 AN: 27078

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

African (AFR) AF: 0.298 AC: 12367 AN: 41486

American (AMR) AF: 0.540 AC: 8258 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1899 AN: 3470

East Asian (EAS) AF: 0.506 AC: 2605 AN: 5150

South Asian (SAS) AF: 0.402 AC: 1940 AN: 4822

European-Finnish (FIN) AF: 0.559 AC: 5908 AN: 10572

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38491 AN: 67962

Other (OTH) AF: 0.495 AC: 1045 AN: 2112

Alfa AF: 0.505 Hom.: 3713

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
PhyloP100		0.83
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: rs2008734; hg19: chr11-73366697; COSMIC: COSV57050294; COSMIC: COSV57050294;