Genetic Variant PLEKHA1:c.343-579T>C (chr10-122412341-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 NM_001001974.4(PLEKHA1):c.343-579T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,022 control chromosomes in the GnomAD database, including 17,973 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 ( 17973 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

PLEKHA1
NM_001001974.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.793

Publications

17 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:

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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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA1	NM_001001974.4 link	c.343-579T>C		intron_variant	Intron 5 of 11	ENST00000368990.8	NP_001001974.1	Q9HB21-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA1	ENST00000368990.8 link	c.343-579T>C		intron_variant	Intron 5 of 11	1	NM_001001974.4	ENSP00000357986.3		Q9HB21-1

Frequencies

GnomAD3 genomes

AF:

0.478

AC:

72560

AN:

151902

Hom.:

17950

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.557

Gnomad ASJ

AF:

0.439

Gnomad EAS

AF:

0.623

Gnomad SAS

AF:

0.544

Gnomad FIN

AF:

0.634

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.483

Gnomad OTH

AF:

0.465

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.478

AC:

72620

AN:

152020

Hom.:

17973

Cov.:

AF XY:

0.490

AC XY:

36382

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.377

AC:

15617

AN:

41446

American (AMR)

AF:

0.557

AC:

8518

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

1523

AN:

3466

East Asian (EAS)

AF:

0.624

AC:

3225

AN:

5172

South Asian (SAS)

AF:

0.546

AC:

2627

AN:

4814

European-Finnish (FIN)

AF:

0.634

AC:

6710

AN:

10582

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.483

AC:

32789

AN:

67950

Other (OTH)

AF:

0.469

AC:

988

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1913

3826

5740

7653

9566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<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:

0.460

Hom.:

4146

Bravo

AF:

0.471

Asia WGS

AF:

0.573

AC:

1988

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.2

(source)

DANN

Benign

0.79

PhyloP100

0.79

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over