10-122387175-A-T

Variant names:

• chr10-122387175-A-T
• rs7902176
• ENST00000392799.7:c.-899A>T

Variant summary

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

The ENST00000392799.7(PLEKHA1):​c.-899A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,602 control chromosomes in the GnomAD database, including 8,066 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 0.31 (8065 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: PLEKHA1 ENST00000392799.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.662
• Publications: 8 publications found

Genes affected

PLEKHA1 (HGNC:14335): (pleckstrin homology domain containing A1) This gene encodes a pleckstrin homology domain-containing adapter protein. The encoded protein is localized to the plasma membrane where it specifically binds phosphatidylinositol 3,4-bisphosphate. This protein may be involved in the formation of signaling complexes in the plasma membrane. Polymorphisms in this gene are associated with age-related macular degeneration. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5.[provided by RefSeq, Sep 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA1	NM_001001974.4	c.-20-6006A>T		intron_variant	Intron 1 of 11	ENST00000368990.8	NP_001001974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.-20-6006A>T		intron_variant	Intron 1 of 11	1	NM_001001974.4	ENSP00000357986.3

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47585 AN: 151482 Hom.: 8067 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.346

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.314 AC: 47600 AN: 151600 Hom.: 8065 Cov.: 32 AF XY: 0.307 AC XY: 22735 AN XY: 74074

African (AFR) AF: 0.200 AC: 8276 AN: 41344

American (AMR) AF: 0.296 AC: 4510 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1374 AN: 3466

East Asian (EAS) AF: 0.196 AC: 1011 AN: 5152

South Asian (SAS) AF: 0.273 AC: 1308 AN: 4794

European-Finnish (FIN) AF: 0.295 AC: 3077 AN: 10444

Middle Eastern (MID) AF: 0.323 AC: 93 AN: 288

European-Non Finnish (NFE) AF: 0.397 AC: 26951 AN: 67850

Other (OTH) AF: 0.345 AC: 724 AN: 2098

Alfa AF: 0.193 Hom.: 421

Bravo AF: 0.308

Asia WGS AF: 0.228 AC: 792 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.6
DANN	Benign	0.70
PhyloP100		0.66
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: rs7902176; hg19: chr10-124146691;