10-122435525-G-C

Variant names:

• chr10-122435525-G-C
• rs4752695
• NR_165160.1:n.7080G>C

Variant summary

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

The NR_165160.1(PLEKHA1):​n.7080G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,150 control chromosomes in the GnomAD database, including 1,626 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 0.14 (1626 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: PLEKHA1 NR_165160.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA1	NR_165160.1	n.7080G>C		non_coding_transcript_exon_variant	Exon 14 of 14
PLEKHA1	NR_165161.1	n.7028G>C		non_coding_transcript_exon_variant	Exon 14 of 14
PLEKHA1	NR_165162.1	n.6893G>C		non_coding_transcript_exon_variant	Exon 12 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21235 AN: 152032 Hom.: 1625 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.138

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 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) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.140 AC: 21260 AN: 152150 Hom.: 1626 Cov.: 31 AF XY: 0.137 AC XY: 10193 AN XY: 74400

African (AFR) AF: 0.184 AC: 7620 AN: 41498

American (AMR) AF: 0.123 AC: 1885 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 556 AN: 3472

East Asian (EAS) AF: 0.182 AC: 939 AN: 5172

South Asian (SAS) AF: 0.182 AC: 875 AN: 4820

European-Finnish (FIN) AF: 0.0720 AC: 762 AN: 10580

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8128 AN: 68000

Other (OTH) AF: 0.137 AC: 289 AN: 2112

Alfa AF: 0.118 Hom.: 167

Bravo AF: 0.143

Asia WGS AF: 0.181 AC: 627 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.60
PhyloP100		1.8

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: rs4752695; hg19: chr10-124195041;