10-122405138-A-G

Position:

• chr10-122405138-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.245-1438A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,146 control chromosomes in the GnomAD database, including 3,135 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 0.20 (3135 hom., cov: 32)
• Consequence: PLEKHA1 NM_001001974.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918

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]

PLEKHA1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA1	NM_001001974.4	c.245-1438A>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.245-1438A>G		intron_variant		1	NM_001001974.4	ENSP00000357986.3

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30144 AN: 152028 Hom.: 3134 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.198 AC: 30157 AN: 152146 Hom.: 3135 Cov.: 32 AF XY: 0.193 AC XY: 14381 AN XY: 74372

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.216

Alfa AF: 0.219 Hom.: 7349

Bravo AF: 0.202

Asia WGS AF: 0.210 AC: 731 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.22
DANN	Benign	0.67

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: rs10082476; hg19: chr10-124164654;