Genetic Variant PLEKHA1:n.12893T>C (chr10-122441338-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NR_165160.1(PLEKHA1):n.12893T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 152,030 control chromosomes in the GnomAD database, including 56,192 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 0.86 ( 56176 hom., cov: 29)

Exomes 𝑓: 0.86 ( 16 hom. )

Consequence

PLEKHA1
NR_165160.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.68

Publications

4 publications found

Variant links:

Genes affected

PLEKHA1 (HGNC:14335): (pleckstrin homology domain containing A1) This gene encodes a pleckstrin homology domain-containing adapter protein. The encoded protein is localized to the plasma membrane where it specifically binds phosphatidylinositol 3,4-bisphosphate. This protein may be involved in the formation of signaling complexes in the plasma membrane. Polymorphisms in this gene are associated with age-related macular degeneration. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5.[provided by RefSeq, Sep 2010]

PLEKHA1 links:

ENSG00000285955 (HGNC:58122):

ENSG00000285955 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=-1.03).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
PLEKHA1	NR_165160.1 link	n.12893T>C	non_coding_transcript_exon_variant	Exon 14 of 14
PLEKHA1	NR_165161.1 link	n.12841T>C	non_coding_transcript_exon_variant	Exon 14 of 14
PLEKHA1	NR_165162.1 link	n.12706T>C	non_coding_transcript_exon_variant	Exon 12 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000285955	ENST00000650300.1 link	n.1853-4706A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.859

AC:

130398

AN:

151870

Hom.:

56119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.877

Gnomad AMI

AF:

0.868

Gnomad AMR

AF:

0.879

Gnomad ASJ

AF:

0.767

Gnomad EAS

AF:

0.941

Gnomad SAS

AF:

0.852

Gnomad FIN

AF:

0.917

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.833

Gnomad OTH

AF:

0.844

GnomAD4 exome

AF:

0.857

AC:

AN:

Hom.:

Cov.:

AF XY:

0.933

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.824

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.859

AC:

130512

AN:

151988

Hom.:

56176

Cov.:

AF XY:

0.864

AC XY:

64221

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.877

AC:

36320

AN:

41408

American (AMR)

AF:

0.880

AC:

13438

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.767

AC:

2659

AN:

3468

East Asian (EAS)

AF:

0.941

AC:

4840

AN:

5144

South Asian (SAS)

AF:

0.852

AC:

4102

AN:

4816

European-Finnish (FIN)

AF:

0.917

AC:

9712

AN:

10588

Middle Eastern (MID)

AF:

0.793

AC:

233

AN:

294

European-Non Finnish (NFE)

AF:

0.833

AC:

56633

AN:

67976

Other (OTH)

AF:

0.846

AC:

1789

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

914

1829

2743

3658

4572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<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:

0.837

Hom.:

14610

Bravo

AF:

0.856

Asia WGS

AF:

0.912

AC:

3172

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.83

(source)

DANN

Benign

0.26

PhyloP100

-1.7

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over