rs4764470

Positions:

• chr12-19189219-A-G
• chr12-19189219-A-T

Variant summary

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

The NM_001256470.2(PLEKHA5):​c.227+56769A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,102 control chromosomes in the GnomAD database, including 39,586 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 0.71 (39586 hom., cov: 32)
• Consequence: PLEKHA5 NM_001256470.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290

Genes affected

PLEKHA5 (HGNC:30036): (pleckstrin homology domain containing A5) Predicted to enable phosphatidylinositol phosphate binding activity. Predicted to act upstream of or within reproductive system development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA5	NM_001256470.2	c.227+56769A>G		intron_variant		ENST00000429027.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA5	ENST00000429027.7	c.227+56769A>G		intron_variant		1	NM_001256470.2	A2

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107882 AN: 151984 Hom.: 39582 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.837

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.709 AC: 107913 AN: 152102 Hom.: 39586 Cov.: 32 AF XY: 0.710 AC XY: 52816 AN XY: 74360

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.646

Gnomad4 FIN AF: 0.837

Gnomad4 NFE AF: 0.806

Gnomad4 OTH AF: 0.723

Alfa AF: 0.785 Hom.: 61730

Bravo AF: 0.697

Asia WGS AF: 0.555 AC: 1938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
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: rs4764470; hg19: chr12-19342153;