11-16994010-T-C

Variant names:

• chr11-16994010-T-C
• rs6486334
• NM_001329630.2:c.221+19979A>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.221+19979A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,126 control chromosomes in the GnomAD database, including 12,665 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 0.40 (12665 hom., cov: 33)
• Consequence: PLEKHA7 NM_001329630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.719
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA7	NM_001329630.2	c.221+19979A>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.221+19979A>G		intron_variant	Intron 3 of 26	5	NM_001329630.2	ENSP00000435389.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60477 AN: 152008 Hom.: 12627 Cov.: 33

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.398 AC: 60571 AN: 152126 Hom.: 12665 Cov.: 33 AF XY: 0.400 AC XY: 29741 AN XY: 74372

African (AFR) AF: 0.482 AC: 20028 AN: 41510

American (AMR) AF: 0.451 AC: 6887 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1621 AN: 3468

East Asian (EAS) AF: 0.571 AC: 2949 AN: 5166

South Asian (SAS) AF: 0.415 AC: 2001 AN: 4826

European-Finnish (FIN) AF: 0.291 AC: 3083 AN: 10584

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.335 AC: 22792 AN: 67972

Other (OTH) AF: 0.400 AC: 846 AN: 2114

Alfa AF: 0.352 Hom.: 5221

Bravo AF: 0.411

Asia WGS AF: 0.504 AC: 1752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.66
PhyloP100		-0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6486334; hg19: chr11-17015557;