rs4757448

Positions:

• chr11-16935072-C-G
• chr11-16935072-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.222-63890G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,160 control chromosomes in the GnomAD database, including 5,812 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 0.25 (5812 hom., cov: 33)
• Consequence: PLEKHA7 NM_001329630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223

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=-0.5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA7	NM_001329630.2	c.222-63890G>C		intron_variant		ENST00000531066.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA7	ENST00000531066.6	c.222-63890G>C		intron_variant		5	NM_001329630.2	A1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38270 AN: 152042 Hom.: 5815 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0533

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.251 AC: 38263 AN: 152160 Hom.: 5812 Cov.: 33 AF XY: 0.242 AC XY: 18039 AN XY: 74390

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.0536

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.244

Alfa AF: 0.304 Hom.: 984

Bravo AF: 0.239

Asia WGS AF: 0.0930 AC: 325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.74

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: rs4757448; hg19: chr11-16956619;