10-122406099-G-A

Variant names:

• chr10-122406099-G-A
• rs6585827
• NM_001001974.4:c.245-477G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 46 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001974.4. 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.245-477G>A		intron	N/A	NP_001001974.1	Q9HB21-1
	PLEKHA1	NM_001377230.1		c.245-477G>A		intron	N/A	NP_001364159.1	Q9HB21-1
	PLEKHA1	NM_001377231.1		c.245-477G>A		intron	N/A	NP_001364160.1	Q9HB21-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHA1	ENST00000368990.8	TSL:1 MANE Select	c.245-477G>A		intron	N/A	ENSP00000357986.3	Q9HB21-1
	PLEKHA1	ENST00000392799.7	TSL:1	c.245-477G>A		intron	N/A	ENSP00000376547.3	Q9HB21-1
	PLEKHA1	ENST00000433307.2	TSL:1	c.245-477G>A		intron	N/A	ENSP00000394416.1	Q9HB21-1

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

African (AFR) AF: 0.376 AC: 15581 AN: 41398

American (AMR) AF: 0.556 AC: 8485 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1503 AN: 3470

East Asian (EAS) AF: 0.623 AC: 3209 AN: 5154

South Asian (SAS) AF: 0.545 AC: 2627 AN: 4822

European-Finnish (FIN) AF: 0.635 AC: 6697 AN: 10550

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32794 AN: 67954

Other (OTH) AF: 0.468 AC: 981 AN: 2098

Alfa AF: 0.487 Hom.: 44374

Bravo AF: 0.470

Asia WGS AF: 0.572 AC: 1988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.68
DANN	Benign	0.43
PhyloP100		-0.18
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: rs6585827; hg19: chr10-124165615;