rs11024074

Variant names:

• chr11-16895672-T-C
• rs11024074
• NM_001329630.2:c.222-24490A>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.222-24490A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,078 control chromosomes in the GnomAD database, including 6,638 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 0.29 (6638 hom., cov: 32)
• Consequence: PLEKHA7 NM_001329630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.97
• Publications: 46 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA7	NM_001329630.2	c.222-24490A>G		intron_variant	Intron 3 of 26	ENST00000531066.6	NP_001316559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA7	ENST00000531066.6	c.222-24490A>G		intron_variant	Intron 3 of 26	5	NM_001329630.2	ENSP00000435389.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44332 AN: 151960 Hom.: 6626 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.292 AC: 44389 AN: 152078 Hom.: 6638 Cov.: 32 AF XY: 0.287 AC XY: 21326 AN XY: 74358

African (AFR) AF: 0.318 AC: 13179 AN: 41466

American (AMR) AF: 0.262 AC: 4000 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1078 AN: 3470

East Asian (EAS) AF: 0.211 AC: 1091 AN: 5172

South Asian (SAS) AF: 0.187 AC: 904 AN: 4822

European-Finnish (FIN) AF: 0.251 AC: 2657 AN: 10584

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20582 AN: 67968

Other (OTH) AF: 0.279 AC: 589 AN: 2108

Alfa AF: 0.296 Hom.: 23361

Bravo AF: 0.294

Asia WGS AF: 0.233 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.012
DANN	Benign	0.62
PhyloP100		-4.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11024074; hg19: chr11-16917219;