NR_165160.1:n.6855A>G

Variant names:

• chr10-122435300-A-G
• rs17564097
• NR_165160.1:n.6855A>G

Variant summary

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

The NR_165160.1(PLEKHA1):​n.6855A>G 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 0.112 in 152,272 control chromosomes in the GnomAD database, including 1,340 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 0.11 (1340 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: PLEKHA1 NR_165160.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA1	NR_165160.1	n.6855A>G		non_coding_transcript_exon_variant	Exon 14 of 14
PLEKHA1	NR_165161.1	n.6803A>G		non_coding_transcript_exon_variant	Exon 14 of 14
PLEKHA1	NR_165162.1	n.6668A>G		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: 0.113 AC: 17132 AN: 152154 Hom.: 1341 Cov.: 31

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0365

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.129

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: 0.112 AC: 17127 AN: 152272 Hom.: 1340 Cov.: 31 AF XY: 0.110 AC XY: 8203 AN XY: 74456

African (AFR) AF: 0.0285 AC: 1186 AN: 41576

American (AMR) AF: 0.117 AC: 1788 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0367 AC: 177 AN: 4824

European-Finnish (FIN) AF: 0.164 AC: 1735 AN: 10596

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11339 AN: 68010

Other (OTH) AF: 0.127 AC: 269 AN: 2114

Alfa AF: 0.135 Hom.: 228

Bravo AF: 0.103

Asia WGS AF: 0.0170 AC: 61 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.62
DANN	Benign	0.78
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: rs17564097; hg19: chr10-124194816;