Genetic Variant NM_021200.3:c.391-151G>A (chr11-73655652-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.831

Publications

12 publications found

Variant links:

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]

PLEKHB1 links:

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ACMG classification

Classification was made for transcript

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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PLEKHB1	NM_021200.3	MANE Select	c.391-151G>A	intron	N/A	NP_067023.1
PLEKHB1	NM_001130034.2		c.334-151G>A	intron	N/A	NP_001123506.1
PLEKHB1	NM_001130033.2		c.390+2638G>A	intron	N/A	NP_001123505.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PLEKHB1	ENST00000354190.10	TSL:1 MANE Select	c.391-151G>A	intron	N/A	ENSP00000346127.5
PLEKHB1	ENST00000398494.8	TSL:1	c.334-151G>A	intron	N/A	ENSP00000381507.4
PLEKHB1	ENST00000398492.8	TSL:1	c.390+2638G>A	intron	N/A	ENSP00000381505.4

Frequencies

GnomAD3 genomes

AF:

0.482

AC:

73201

AN:

151934

Hom.:

18770

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

5825

11650

17475

23300

29125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1030

2060

3090

4120

5150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.482

AC:

73238

AN:

152054

Hom.:

18779

Cov.:

AF XY:

0.482

AC XY:

35797

AN XY:

74312

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1860

3719

5579

7438

9298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

658

1316

1974

2632

3290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

0.83

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over