rs435206

Positions:

• chr11-16881631-C-A
• chr11-16881631-C-T

Variant summary

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

The NM_001329630.2(PLEKHA7):​c.222-10449G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,148 control chromosomes in the GnomAD database, including 1,103 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 0.11 (1102 hom., cov: 32)
  • Exomes 𝑓: 0.093 (1 hom.)
• Consequence: PLEKHA7 NM_001329630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA7	NM_001329630.2	c.222-10449G>T		intron_variant		ENST00000531066.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA7	ENST00000531066.6	c.222-10449G>T		intron_variant		5	NM_001329630.2	A1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16581 AN: 151976 Hom.: 1103 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0926

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.137

GnomAD4 exome AF: 0.0926 AC: 5 AN: 54 Hom.: 1 Cov.: 0 AF XY: 0.0652 AC XY: 3 AN XY: 46

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.109 AC: 16582 AN: 152094 Hom.: 1102 Cov.: 32 AF XY: 0.109 AC XY: 8083 AN XY: 74326

Gnomad4 AFR AF: 0.0348

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0926

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.135

Alfa AF: 0.0516 Hom.: 51

Bravo AF: 0.115

Asia WGS AF: 0.135 AC: 469 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.90
DANN	Benign	0.61

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: rs435206; hg19: chr11-16903178;