rs2421016

Variant names:

• chr10-122407996-C-T
• rs2421016
• NM_001001974.4:c.342+1323C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001001974.4(PLEKHA1):​c.342+1323C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,022 control chromosomes in the GnomAD database, including 16,980 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (16980 hom., cov: 33)
• Consequence: PLEKHA1 NM_001001974.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.38

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=-0.24).
• BP6: Variant 10-122407996-C-T is Benign according to our data. Variant chr10-122407996-C-T is described in ClinVar as [Benign]. Clinvar id is 1238542.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA1	NM_001001974.4	c.342+1323C>T		intron_variant	Intron 5 of 11	ENST00000368990.8	NP_001001974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.342+1323C>T		intron_variant	Intron 5 of 11	1	NM_001001974.4	ENSP00000357986.3

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69797 AN: 151904 Hom.: 16961 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.459 AC: 69848 AN: 152022 Hom.: 16980 Cov.: 33 AF XY: 0.471 AC XY: 35032 AN XY: 74318

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.456

Alfa AF: 0.476 Hom.: 4982

Bravo AF: 0.450

Asia WGS AF: 0.562 AC: 1953 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 18, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30181159) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	14
DANN	Benign	0.84

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: rs2421016; hg19: chr10-124167512;