10-122412341-T-C

Variant names:

• chr10-122412341-T-C
• rs7097701
• NM_001001974.4:c.343-579T>C

Variant summary

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

The NM_001001974.4(PLEKHA1):​c.343-579T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,022 control chromosomes in the GnomAD database, including 17,973 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 0.48 (17973 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: PLEKHA1 NM_001001974.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.793
• Publications: 17 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 (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA1	NM_001001974.4	c.343-579T>C		intron_variant	Intron 5 of 11	ENST00000368990.8	NP_001001974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA1	ENST00000368990.8	c.343-579T>C		intron_variant	Intron 5 of 11	1	NM_001001974.4	ENSP00000357986.3

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72560 AN: 151902 Hom.: 17950 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.465

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

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: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.478 AC: 72620 AN: 152020 Hom.: 17973 Cov.: 32 AF XY: 0.490 AC XY: 36382 AN XY: 74322

African (AFR) AF: 0.377 AC: 15617 AN: 41446

American (AMR) AF: 0.557 AC: 8518 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1523 AN: 3466

East Asian (EAS) AF: 0.624 AC: 3225 AN: 5172

South Asian (SAS) AF: 0.546 AC: 2627 AN: 4814

European-Finnish (FIN) AF: 0.634 AC: 6710 AN: 10582

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32789 AN: 67950

Other (OTH) AF: 0.469 AC: 988 AN: 2108

Alfa AF: 0.460 Hom.: 4146

Bravo AF: 0.471

Asia WGS AF: 0.573 AC: 1988 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.79
PhyloP100		0.79
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: rs7097701; hg19: chr10-124171857;