rs4565845

chr10-122399534-A-Cchr10-122399534-A-T

Variant summary

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

The NM_001001974.4(PLEKHA1):c.199-809A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 151,984 control chromosomes in the GnomAD database, including 3,144 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 0.19 (3144 hom., cov: 31)
• Consequence: PLEKHA1 NM_001001974.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA1	NM_001001974.4	c.199-809A>C		intron_variant		ENST00000368990.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.199-809A>C		intron_variant		1	NM_001001974.4	P3

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28726 AN: 151866 Hom.: 3135 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.189 AC: 28766 AN: 151984 Hom.: 3144 Cov.: 31 AF XY: 0.193 AC XY: 14353 AN XY: 74280

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.170

Alfa AF: 0.154 Hom.: 493

Bravo AF: 0.197

Asia WGS AF: 0.297 AC: 1028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	11
Dann	Benign	0.72

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: rs4565845; hg19: chr10-124159050;