rs10399971

chr10-122396329-T-C

Variant summary

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

The NM_001001974.4(PLEKHA1):c.142-1589T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.093 in 152,162 control chromosomes in the GnomAD database, including 778 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 0.093 (778 hom., cov: 32)
• Consequence: PLEKHA1 NM_001001974.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.740

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA1	NM_001001974.4	c.142-1589T>C		intron_variant		ENST00000368990.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.142-1589T>C		intron_variant		1	NM_001001974.4	P3

Frequencies

GnomAD3 genomes AF: 0.0931 AC: 14150 AN: 152044 Hom.: 779 Cov.: 32

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.0923

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.0676

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0930 AC: 14145 AN: 152162 Hom.: 778 Cov.: 32 AF XY: 0.0911 AC XY: 6776 AN XY: 74396

Gnomad4 AFR AF: 0.0620

Gnomad4 AMR AF: 0.0921

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0676

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0985 Hom.: 112

Bravo AF: 0.0895

Asia WGS AF: 0.0830 AC: 286 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	9.0
Dann	Benign	0.70

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: rs10399971; hg19: chr10-124155845;