rs389967

Variant names:

• chr11-16853063-G-A
• rs389967
• NM_001329630.2:c.523-708C>T

Variant summary

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

The NM_001329630.2(PLEKHA7):​c.523-708C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,198 control chromosomes in the GnomAD database, including 891 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 0.10 (891 hom., cov: 33)
• Consequence: PLEKHA7 NM_001329630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA7	NM_001329630.2	c.523-708C>T		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.523-708C>T		intron_variant	Intron 6 of 26	5	NM_001329630.2	ENSP00000435389.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15628 AN: 152080 Hom.: 892 Cov.: 33

Gnomad AFR AF: 0.0657

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0643

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.103 AC: 15631 AN: 152198 Hom.: 891 Cov.: 33 AF XY: 0.101 AC XY: 7533 AN XY: 74414

African (AFR) AF: 0.0656 AC: 2726 AN: 41534

American (AMR) AF: 0.144 AC: 2192 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 498 AN: 3472

East Asian (EAS) AF: 0.159 AC: 822 AN: 5180

South Asian (SAS) AF: 0.118 AC: 568 AN: 4828

European-Finnish (FIN) AF: 0.0643 AC: 681 AN: 10592

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7799 AN: 68004

Other (OTH) AF: 0.117 AC: 247 AN: 2108

Alfa AF: 0.115 Hom.: 252

Bravo AF: 0.110

Asia WGS AF: 0.129 AC: 449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.6
DANN	Benign	0.63
PhyloP100		1.2
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: rs389967; hg19: chr11-16874610;