rs11200621

Variant names:

• chr10-122419462-A-G
• rs11200621
• NM_001001974.4:c.681+1494A>G

Variant summary

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

The NM_001001974.4(PLEKHA1):​c.681+1494A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,220 control chromosomes in the GnomAD database, including 1,496 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 0.12 (1496 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLEKHA1 NM_001001974.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA1	NM_001001974.4	c.681+1494A>G		intron_variant	Intron 8 of 11	ENST00000368990.8	NP_001001974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.681+1494A>G		intron_variant	Intron 8 of 11	1	NM_001001974.4	ENSP00000357986.3

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18722 AN: 152102 Hom.: 1491 Cov.: 32

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0862

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.125

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.123 AC: 18742 AN: 152220 Hom.: 1496 Cov.: 32 AF XY: 0.126 AC XY: 9371 AN XY: 74442

Gnomad4 AFR AF: 0.0360

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0858

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.132

Alfa AF: 0.154 Hom.: 3398

Bravo AF: 0.127

Asia WGS AF: 0.114 AC: 395 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.86
DANN	Benign	0.38

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: rs11200621; hg19: chr10-124178978;