rs591804

Variant names:

• chr11-73652165-G-A
• rs591804
• NM_021200.3:c.350+275G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021200.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHB1	NM_021200.3	MANE Select	c.350+275G>A		intron	N/A	NP_067023.1	Q9UF11-1
	PLEKHB1	NM_001130034.2		c.293+275G>A		intron	N/A	NP_001123506.1	Q9UF11-3
	PLEKHB1	NM_001130033.2		c.350+275G>A		intron	N/A	NP_001123505.1	Q9UF11-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHB1	ENST00000354190.10	TSL:1 MANE Select	c.350+275G>A		intron	N/A	ENSP00000346127.5	Q9UF11-1
	PLEKHB1	ENST00000398494.8	TSL:1	c.293+275G>A		intron	N/A	ENSP00000381507.4	Q9UF11-3
	PLEKHB1	ENST00000398492.8	TSL:1	c.350+275G>A		intron	N/A	ENSP00000381505.4	Q9UF11-2

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

African (AFR) AF: 0.533 AC: 4817 AN: 9040

American (AMR) AF: 0.649 AC: 7538 AN: 11610

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 6592 AN: 9890

East Asian (EAS) AF: 0.681 AC: 13308 AN: 19534

South Asian (SAS) AF: 0.636 AC: 23404 AN: 36806

European-Finnish (FIN) AF: 0.688 AC: 13035 AN: 18950

Middle Eastern (MID) AF: 0.637 AC: 869 AN: 1364

European-Non Finnish (NFE) AF: 0.672 AC: 126510 AN: 188340

Other (OTH) AF: 0.655 AC: 11957 AN: 18242

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

African (AFR) AF: 0.529 AC: 21915 AN: 41462

American (AMR) AF: 0.650 AC: 9922 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2353 AN: 3472

East Asian (EAS) AF: 0.689 AC: 3557 AN: 5164

South Asian (SAS) AF: 0.625 AC: 3016 AN: 4826

European-Finnish (FIN) AF: 0.687 AC: 7269 AN: 10582

Middle Eastern (MID) AF: 0.610 AC: 177 AN: 290

European-Non Finnish (NFE) AF: 0.670 AC: 45508 AN: 67934

Other (OTH) AF: 0.612 AC: 1292 AN: 2110

Alfa AF: 0.651 Hom.: 12677

Bravo AF: 0.619

Asia WGS AF: 0.646 AC: 2245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.36
PhyloP100		-0.39
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: rs591804; hg19: chr11-73363210;