NM_001001974.4:c.198+803A>C

Variant names:

• chr10-122398777-A-C
• rs4598609
• NM_001001974.4:c.198+803A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001001974.4(PLEKHA1):​c.198+803A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 152,194 control chromosomes in the GnomAD database, including 252 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 0.051 (252 hom., cov: 32)
• Consequence: PLEKHA1 NM_001001974.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA1	NM_001001974.4	c.198+803A>C		intron_variant	Intron 3 of 11	ENST00000368990.8	NP_001001974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.198+803A>C		intron_variant	Intron 3 of 11	1	NM_001001974.4	ENSP00000357986.3

Frequencies

GnomAD3 genomes AF: 0.0509 AC: 7738 AN: 152076 Hom.: 251 Cov.: 32

Gnomad AFR AF: 0.0191

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.0874

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0626

Gnomad OTH AF: 0.0508

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

GnomAD4 genome AF: 0.0509 AC: 7746 AN: 152194 Hom.: 252 Cov.: 32 AF XY: 0.0520 AC XY: 3873 AN XY: 74422

African (AFR) AF: 0.0190 AC: 791 AN: 41542

American (AMR) AF: 0.0559 AC: 856 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3470

East Asian (EAS) AF: 0.139 AC: 721 AN: 5180

South Asian (SAS) AF: 0.0873 AC: 421 AN: 4822

European-Finnish (FIN) AF: 0.0464 AC: 491 AN: 10584

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0626 AC: 4254 AN: 67984

Other (OTH) AF: 0.0531 AC: 112 AN: 2108

Alfa AF: 0.0567 Hom.: 603

Bravo AF: 0.0506

Asia WGS AF: 0.126 AC: 438 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.68
DANN	Benign	0.71
PhyloP100		-0.44
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: rs4598609; hg19: chr10-124158293;