rs2292625

Positions:

• chr10-122426851-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418

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=-0.84).
• 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/exons	MANE	UniProt
PLEKHA1	NM_001001974.4	c.811-91G>A		intron_variant		ENST00000368990.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.811-91G>A		intron_variant		1	NM_001001974.4	P3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22252 AN: 152078 Hom.: 1773 Cov.: 32

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

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.0913

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.0515

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.0825

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.163

GnomAD4 genome AF: 0.146 AC: 22254 AN: 152196 Hom.: 1775 Cov.: 32 AF XY: 0.140 AC XY: 10451 AN XY: 74434

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.0586

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0829

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.160

Alfa AF: 0.151 Hom.: 283

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
DANN	Benign	0.32

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: rs2292625; hg19: chr10-124186367;