Genetic Variant PLEKHA1:c.-899A>T (chr10-122387175-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000392799.7(PLEKHA1):c.-899A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,602 control chromosomes in the GnomAD database, including 8,066 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 0.31 ( 8065 hom., cov: 32)

Exomes 𝑓: 1.0 ( 1 hom. )

Consequence

PLEKHA1
ENST00000392799.7 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.662

Publications

8 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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new If you want to explore the variant's impact on the transcript ENST00000392799.7, 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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000392799.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLEKHA1	NM_001001974.4	MANE Select	c.-20-6006A>T	intron	N/A	NP_001001974.1	Q9HB21-1
PLEKHA1	NM_001377230.1		c.-86-5128A>T	intron	N/A	NP_001364159.1	Q9HB21-1
PLEKHA1	NM_001377231.1		c.-836-480A>T	intron	N/A	NP_001364160.1	Q9HB21-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PLEKHA1	ENST00000392799.7	TSL:1	c.-899A>T	5_prime_UTR	Exon 1 of 13	ENSP00000376547.3	Q9HB21-1
PLEKHA1	ENST00000368990.8	TSL:1 MANE Select	c.-20-6006A>T	intron	N/A	ENSP00000357986.3	Q9HB21-1
PLEKHA1	ENST00000919450.1		c.-20-6006A>T	intron	N/A	ENSP00000589509.1

Frequencies

GnomAD3 genomes

AF:

0.314

AC:

47585

AN:

151482

Hom.:

8067

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.303

Gnomad AMR

AF:

0.296

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.272

Gnomad FIN

AF:

0.295

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.346

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

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:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.314

AC:

47600

AN:

151600

Hom.:

8065

Cov.:

AF XY:

0.307

AC XY:

22735

AN XY:

74074

show subpopulations

African (AFR)

AF:

0.200

AC:

8276

AN:

41344

American (AMR)

AF:

0.296

AC:

4510

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.396

AC:

1374

AN:

3466

East Asian (EAS)

AF:

0.196

AC:

1011

AN:

5152

South Asian (SAS)

AF:

0.273

AC:

1308

AN:

4794

European-Finnish (FIN)

AF:

0.295

AC:

3077

AN:

10444

Middle Eastern (MID)

AF:

0.323

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.397

AC:

26951

AN:

67850

Other (OTH)

AF:

0.345

AC:

724

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1670

3341

5011

6682

8352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.193

Hom.:

421

Bravo

AF:

0.308

Asia WGS

AF:

0.228

AC:

792

AN:

3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.6

(source)

DANN

Benign

0.70

PhyloP100

0.66

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over