rs12362925

Variant names:

• chr11-16853872-T-C
• rs12362925
• NM_001329630.2:c.522+1017A>G

Variant summary

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

The NM_001329630.2(PLEKHA7):​c.522+1017A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 152,244 control chromosomes in the GnomAD database, including 652 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 0.075 (652 hom., cov: 32)
• Consequence: PLEKHA7 NM_001329630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 4 publications found

Genes affected

PLEKHA7 (HGNC:27049): (pleckstrin homology domain containing A7) Enables delta-catenin binding activity. Involved in epithelial cell-cell adhesion; pore complex assembly; and zonula adherens maintenance. Located in several cellular components, including centrosome; nucleoplasm; and zonula adherens. Part of pore complex. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA7	NM_001329630.2	c.522+1017A>G		intron_variant	Intron 6 of 26	ENST00000531066.6	NP_001316559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA7	ENST00000531066.6	c.522+1017A>G		intron_variant	Intron 6 of 26	5	NM_001329630.2	ENSP00000435389.1

Frequencies

GnomAD3 genomes AF: 0.0756 AC: 11497 AN: 152126 Hom.: 652 Cov.: 32

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0508

Gnomad ASJ AF: 0.0790

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0194

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0564

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

GnomAD4 genome AF: 0.0755 AC: 11494 AN: 152244 Hom.: 652 Cov.: 32 AF XY: 0.0750 AC XY: 5580 AN XY: 74430

African (AFR) AF: 0.0204 AC: 847 AN: 41552

American (AMR) AF: 0.0508 AC: 776 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0790 AC: 274 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4830

European-Finnish (FIN) AF: 0.136 AC: 1440 AN: 10596

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7845 AN: 68008

Other (OTH) AF: 0.0558 AC: 118 AN: 2116

Alfa AF: 0.102 Hom.: 457

Bravo AF: 0.0656

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.46
PhyloP100		0.075
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: rs12362925; hg19: chr11-16875419;