rs7926335

Variant names:

• chr11-16896322-C-T
• rs7926335
• NM_001329630.2:c.222-25140G>A

Variant summary

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

The NM_001329630.2(PLEKHA7):​c.222-25140G>A 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 152,080 control chromosomes in the GnomAD database, including 4,968 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 (4968 hom., cov: 32)
• Consequence: PLEKHA7 NM_001329630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.646
• Publications: 12 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 (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA7	NM_001329630.2	c.222-25140G>A		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.222-25140G>A		intron_variant	Intron 3 of 26	5	NM_001329630.2	ENSP00000435389.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38191 AN: 151962 Hom.: 4960 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.251 AC: 38233 AN: 152080 Hom.: 4968 Cov.: 32 AF XY: 0.248 AC XY: 18477 AN XY: 74366

African (AFR) AF: 0.249 AC: 10324 AN: 41492

American (AMR) AF: 0.247 AC: 3772 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1012 AN: 3470

East Asian (EAS) AF: 0.167 AC: 862 AN: 5158

South Asian (SAS) AF: 0.138 AC: 666 AN: 4814

European-Finnish (FIN) AF: 0.233 AC: 2466 AN: 10578

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.270 AC: 18346 AN: 67964

Other (OTH) AF: 0.241 AC: 508 AN: 2112

Alfa AF: 0.272 Hom.: 893

Bravo AF: 0.255

Asia WGS AF: 0.185 AC: 645 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	3.4
DANN	Benign	0.66
PhyloP100		0.65
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: rs7926335; hg19: chr11-16917869;