rs10488084

Variant names:

• chr7-30043405-A-C
• rs10488084
• NM_001197026.2:c.41-1680A>C

Variant summary

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

The NM_001197026.2(PLEKHA8):​c.41-1680A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0973 in 152,194 control chromosomes in the GnomAD database, including 889 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 0.097 (889 hom., cov: 32)
• Consequence: PLEKHA8 NM_001197026.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.562
• Publications: 5 publications found

Genes affected

PLEKHA8 (HGNC:30037): (pleckstrin homology domain containing A8) Enables several functions, including ceramide binding activity; glycolipid transfer activity; and phosphatidylinositol-4-phosphate binding activity. Involved in ER to Golgi ceramide transport. Located in nucleoplasm and trans-Golgi network. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLEKHA8	NM_001197026.2	c.41-1680A>C		intron_variant	Intron 1 of 13	ENST00000449726.6	NP_001183955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLEKHA8	ENST00000449726.6	c.41-1680A>C		intron_variant	Intron 1 of 13	1	NM_001197026.2	ENSP00000397947.1

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14778 AN: 152076 Hom.: 888 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.0463

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.0832

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

GnomAD4 genome AF: 0.0973 AC: 14806 AN: 152194 Hom.: 889 Cov.: 32 AF XY: 0.0991 AC XY: 7370 AN XY: 74400

African (AFR) AF: 0.142 AC: 5876 AN: 41508

American (AMR) AF: 0.0517 AC: 791 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 180 AN: 3468

East Asian (EAS) AF: 0.0561 AC: 291 AN: 5184

South Asian (SAS) AF: 0.0464 AC: 224 AN: 4830

European-Finnish (FIN) AF: 0.170 AC: 1795 AN: 10588

Middle Eastern (MID) AF: 0.106 AC: 31 AN: 292

European-Non Finnish (NFE) AF: 0.0791 AC: 5377 AN: 68000

Other (OTH) AF: 0.0828 AC: 175 AN: 2114

Alfa AF: 0.0806 Hom.: 2594

Bravo AF: 0.0912

Asia WGS AF: 0.0660 AC: 228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.50
PhyloP100		0.56
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: rs10488084; hg19: chr7-30083021;