rs4311997

Positions:

• chr10-122419783-C-T

Variant summary

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

The NM_001001974.4(PLEKHA1):​c.681+1815C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,998 control chromosomes in the GnomAD database, including 17,629 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 0.47 (17629 hom., cov: 32)
  • Failed GnomAD Quality Control
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHA1	NM_001001974.4	c.681+1815C>T		intron_variant		ENST00000368990.8	NP_001001974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.681+1815C>T		intron_variant		1	NM_001001974.4	ENSP00000357986.3

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71650 AN: 151880 Hom.: 17606 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.460

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.472 AC: 71712 AN: 151998 Hom.: 17629 Cov.: 32 AF XY: 0.484 AC XY: 35928 AN XY: 74284

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.463

Alfa AF: 0.487 Hom.: 2770

Bravo AF: 0.464

Asia WGS AF: 0.572 AC: 1985 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.63

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: rs4311997; hg19: chr10-124179299;