rs2292623

Variant names:

• chr10-122426611-A-G
• rs2292623
• NM_001001974.4:c.811-331A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021622.5(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_021622.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021622.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA1	NM_001001974.4	MANE Select	c.811-331A>G		intron	N/A	NP_001001974.1
	PLEKHA1	NM_001377230.1		c.811-331A>G		intron	N/A	NP_001364159.1
	PLEKHA1	NM_001377231.1		c.811-331A>G		intron	N/A	NP_001364160.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA1	ENST00000368990.8	TSL:1 MANE Select	c.811-331A>G		intron	N/A	ENSP00000357986.3
	PLEKHA1	ENST00000392799.7	TSL:1	c.811-331A>G		intron	N/A	ENSP00000376547.3
	PLEKHA1	ENST00000433307.2	TSL:1	c.811-331A>G		intron	N/A	ENSP00000394416.1

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

African (AFR) AF: 0.425 AC: 17616 AN: 41472

American (AMR) AF: 0.148 AC: 2257 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 568 AN: 3460

East Asian (EAS) AF: 0.180 AC: 930 AN: 5172

South Asian (SAS) AF: 0.183 AC: 884 AN: 4824

European-Finnish (FIN) AF: 0.0717 AC: 760 AN: 10604

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.120 AC: 8187 AN: 67990

Other (OTH) AF: 0.188 AC: 397 AN: 2116

Alfa AF: 0.149 Hom.: 6060

Bravo AF: 0.222

Asia WGS AF: 0.198 AC: 687 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.62
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2292623; hg19: chr10-124186127;