dbSNP rs3981351: PLEKHS1:c.28+56G>A (chr10-113755361-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_001193434.2(PLEKHS1):c.-281G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,578,962 control chromosomes in the GnomAD database, including 440,173 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 0.73 ( 40357 hom., cov: 31)

Exomes 𝑓: 0.75 ( 399816 hom. )

Consequence

PLEKHS1
NM_001193434.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0490

Publications

24 publications found

Variant links:

Genes affected

PLEKHS1 (HGNC:26285): (pleckstrin homology domain containing S1)

PLEKHS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001193434.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193434.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLEKHS1	NM_001395068.1	MANE Select	c.28+56G>A	intron	N/A	NP_001381997.1	Q5SXH7-6
PLEKHS1	NM_001193434.2		c.-281G>A	5_prime_UTR	Exon 2 of 13	NP_001180363.1	Q5SXH7-3
PLEKHS1	NM_001193435.2		c.-85G>A	5_prime_UTR	Exon 2 of 11	NP_001180364.1	Q5SXH7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLEKHS1	ENST00000694986.1	MANE Select	c.28+56G>A	intron	N/A	ENSP00000511629.1	Q5SXH7-6
PLEKHS1	ENST00000369312.9	TSL:2	c.-281G>A	5_prime_UTR	Exon 2 of 13	ENSP00000358318.4	Q5SXH7-3
PLEKHS1	ENST00000619563.5	TSL:5	c.-85G>A	5_prime_UTR	Exon 2 of 11	ENSP00000483759.1	Q5SXH7-3

Frequencies

GnomAD3 genomes

AF:

0.727

AC:

110450

AN:

151880

Hom.:

40322

Cov.:

show subpopulations

Gnomad AFR

AF:

0.683

Gnomad AMI

AF:

0.599

Gnomad AMR

AF:

0.753

Gnomad ASJ

AF:

0.813

Gnomad EAS

AF:

0.584

Gnomad SAS

AF:

0.765

Gnomad FIN

AF:

0.743

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.750

Gnomad OTH

AF:

0.750

GnomAD4 exome

AF:

0.747

AC:

1066388

AN:

1426966

Hom.:

399816

Cov.:

AF XY:

0.749

AC XY:

530413

AN XY:

708012

show subpopulations

African (AFR)

AF:

0.681

AC:

21859

AN:

32120

American (AMR)

AF:

0.729

AC:

27785

AN:

38116

Ashkenazi Jewish (ASJ)

AF:

0.802

AC:

19386

AN:

24182

East Asian (EAS)

AF:

0.565

AC:

21851

AN:

38708

South Asian (SAS)

AF:

0.776

AC:

61922

AN:

79776

European-Finnish (FIN)

AF:

0.744

AC:

38892

AN:

52250

Middle Eastern (MID)

AF:

0.772

AC:

4343

AN:

5624

European-Non Finnish (NFE)

AF:

0.753

AC:

825978

AN:

1097206

Other (OTH)

AF:

0.752

AC:

44372

AN:

58984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

12534

25067

37601

50134

62668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20184

40368

60552

80736

100920

<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:

0.727

AC:

110536

AN:

151996

Hom.:

40357

Cov.:

AF XY:

0.728

AC XY:

54078

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.683

AC:

28278

AN:

41392

American (AMR)

AF:

0.753

AC:

11508

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.813

AC:

2818

AN:

3466

East Asian (EAS)

AF:

0.584

AC:

3011

AN:

5156

South Asian (SAS)

AF:

0.765

AC:

3685

AN:

4816

European-Finnish (FIN)

AF:

0.743

AC:

7850

AN:

10572

Middle Eastern (MID)

AF:

0.823

AC:

242

AN:

294

European-Non Finnish (NFE)

AF:

0.750

AC:

51014

AN:

67990

Other (OTH)

AF:

0.749

AC:

1584

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1540

3080

4621

6161

7701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

846

1692

2538

3384

4230

<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:

0.741

Hom.:

65339

Bravo

AF:

0.726

Asia WGS

AF:

0.710

AC:

2470

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.4

(source)

DANN

Benign

0.60

PhyloP100

0.049

Mutation Taster

=300/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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