rs4764470

Variant names:

• chr12-19189219-A-G
• rs4764470
• NM_001256470.2:c.227+56769A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLEKHA5	NM_001256470.2	c.227+56769A>G		intron_variant	Intron 3 of 31	ENST00000429027.7	NP_001243399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA5	ENST00000429027.7	c.227+56769A>G		intron_variant	Intron 3 of 31	1	NM_001256470.2	ENSP00000404296.2

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

African (AFR) AF: 0.519 AC: 21515 AN: 41480

American (AMR) AF: 0.767 AC: 11720 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2743 AN: 3472

East Asian (EAS) AF: 0.522 AC: 2692 AN: 5156

South Asian (SAS) AF: 0.646 AC: 3113 AN: 4822

European-Finnish (FIN) AF: 0.837 AC: 8849 AN: 10576

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54778 AN: 68004

Other (OTH) AF: 0.723 AC: 1529 AN: 2114

Alfa AF: 0.782 Hom.: 73449

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
PhyloP100		-0.029
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: rs4764470; hg19: chr12-19342153;