rs4146894

chr10-122395865-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001974.4(PLEKHA1):c.142-2053C>T 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 151,738 control chromosomes in the GnomAD database, including 17,950 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 (17950 hom., cov: 31)
• Consequence: PLEKHA1 NM_001001974.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA1	NM_001001974.4	c.142-2053C>T		intron_variant		ENST00000368990.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.142-2053C>T		intron_variant		1	NM_001001974.4	P3

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72499 AN: 151618 Hom.: 17928 Cov.: 31

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.466

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.478 AC: 72560 AN: 151738 Hom.: 17950 Cov.: 31 AF XY: 0.490 AC XY: 36352 AN XY: 74176

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.469

Alfa AF: 0.495 Hom.: 32092

Bravo AF: 0.472

Asia WGS AF: 0.566 AC: 1965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.8
Dann	Benign	0.65

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

LitVar

Other links and lift over

dbSNP: rs4146894; hg19: chr10-124155381;