rs4612730

Positions:

• chr10-122416936-G-A

Variant summary

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

The NM_001001974.4(PLEKHA1):​c.612+934G>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 153,858 control chromosomes in the GnomAD database, including 18,122 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 (17813 hom., cov: 29)
  • Exomes 𝑓: 0.49 (309 hom.)
• Consequence: PLEKHA1 NM_001001974.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.428

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA1	NM_001001974.4	c.612+934G>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.612+934G>A		intron_variant		1	NM_001001974.4	ENSP00000357986.3

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72057 AN: 151252 Hom.: 17791 Cov.: 29

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.461

GnomAD3 exomes AF: 0.470 AC: 2704 AN: 5750 Hom.: 630 AF XY: 0.467 AC XY: 1263 AN XY: 2704

Gnomad AFR exome AF: 0.360

Gnomad AMR exome AF: 0.538

Gnomad ASJ exome AF: 0.489

Gnomad EAS exome AF: 0.583

Gnomad SAS exome AF: 0.519

Gnomad NFE exome AF: 0.472

Gnomad OTH exome AF: 0.515

GnomAD4 exome AF: 0.489 AC: 1217 AN: 2488 Hom.: 309 Cov.: 0 AF XY: 0.500 AC XY: 641 AN XY: 1282

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.833

Gnomad4 ASJ exome AF: 0.500

Gnomad4 SAS exome AF: 0.478

Gnomad4 FIN exome AF: 0.602

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.417

GnomAD4 genome AF: 0.476 AC: 72118 AN: 151370 Hom.: 17813 Cov.: 29 AF XY: 0.488 AC XY: 36093 AN XY: 73914

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.464

Alfa AF: 0.498 Hom.: 2421

Bravo AF: 0.469

Asia WGS AF: 0.577 AC: 2004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4612730; hg19: chr10-124176452; COSMIC: COSV64569134; COSMIC: COSV64569134;