rs2292623

Positions:

• chr10-122426611-A-G

Variant summary

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

The NM_001001974.4(PLEKHA1):​c.811-331A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,132 control chromosomes in the GnomAD database, including 4,799 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 0.21 (4799 hom., cov: 32)
• Consequence: PLEKHA1 NM_001001974.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

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 (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA1	NM_001001974.4	c.811-331A>G		intron_variant		ENST00000368990.8	NP_001001974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.811-331A>G		intron_variant		1	NM_001001974.4	ENSP00000357986.3

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31758 AN: 152014 Hom.: 4782 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0717

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.209 AC: 31805 AN: 152132 Hom.: 4799 Cov.: 32 AF XY: 0.205 AC XY: 15229 AN XY: 74412

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.0717

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.188

Alfa AF: 0.132 Hom.: 2733

Bravo AF: 0.222

Asia WGS AF: 0.198 AC: 687 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.62

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: rs2292623; hg19: chr10-124186127;