rs6585827

Positions:

• chr10-122406099-G-A
• chr10-122406099-G-C

Variant summary

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

The NM_001001974.4(PLEKHA1):​c.245-477G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,904 control chromosomes in the GnomAD database, including 17,926 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 0.48 (17926 hom., cov: 31)
• Consequence: PLEKHA1 NM_001001974.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA1	NM_001001974.4	c.245-477G>A		intron_variant		ENST00000368990.8	NP_001001974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.245-477G>A		intron_variant		1	NM_001001974.4	ENSP00000357986	P3

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72441 AN: 151786 Hom.: 17903 Cov.: 31

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.477 AC: 72503 AN: 151904 Hom.: 17926 Cov.: 31 AF XY: 0.489 AC XY: 36314 AN XY: 74260

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.623

Gnomad4 SAS AF: 0.545

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.468

Alfa AF: 0.495 Hom.: 28609

Bravo AF: 0.470

Asia WGS AF: 0.572 AC: 1988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.68
DANN	Benign	0.43

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: rs6585827; hg19: chr10-124165615;