Genetic Variant PLEKHA1:c.811-91G>A (chr10-122426851-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_001001974.4(PLEKHA1):c.811-91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,117,128 control chromosomes in the GnomAD database, including 15,229 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 0.15 ( 1775 hom., cov: 32)

Exomes 𝑓: 0.16 ( 13454 hom. )

Consequence

PLEKHA1
NM_001001974.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.418

Publications

5 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA1	NM_001001974.4 link	c.811-91G>A		intron_variant	Intron 10 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.811-91G>A		intron_variant	Intron 10 of 11	1	NM_001001974.4	ENSP00000357986.3		Q9HB21-1

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

22252

AN:

152078

Hom.:

1773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.0585

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.0829

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.162

GnomAD4 exome

AF:

0.162

AC:

156340

AN:

964932

Hom.:

13454

AF XY:

0.162

AC XY:

79104

AN XY:

487768

show subpopulations

African (AFR)

AF:

0.138

AC:

3008

AN:

21826

American (AMR)

AF:

0.0913

AC:

2498

AN:

27348

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

4765

AN:

19758

East Asian (EAS)

AF:

0.0515

AC:

1787

AN:

34692

South Asian (SAS)

AF:

0.154

AC:

9900

AN:

64194

European-Finnish (FIN)

AF:

0.0825

AC:

3731

AN:

45240

Middle Eastern (MID)

AF:

0.216

AC:

775

AN:

3592

European-Non Finnish (NFE)

AF:

0.174

AC:

122841

AN:

705122

Other (OTH)

AF:

0.163

AC:

7035

AN:

43160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

6171

12342

18512

24683

30854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3776

7552

11328

15104

18880

<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:

0.146

AC:

22254

AN:

152196

Hom.:

1775

Cov.:

AF XY:

0.140

AC XY:

10451

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.139

AC:

5767

AN:

41514

American (AMR)

AF:

0.121

AC:

1854

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

822

AN:

3470

East Asian (EAS)

AF:

0.0586

AC:

304

AN:

5188

South Asian (SAS)

AF:

0.149

AC:

717

AN:

4824

European-Finnish (FIN)

AF:

0.0829

AC:

879

AN:

10598

Middle Eastern (MID)

AF:

0.204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.168

AC:

11388

AN:

67988

Other (OTH)

AF:

0.160

AC:

338

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

989

1978

2966

3955

4944

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<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:

0.151

Hom.:

287

Bravo

AF:

0.150

Asia WGS

AF:

0.0890

AC:

311

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.61

(source)

DANN

Benign

0.32

PhyloP100

-0.42

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