rs4902496

Positions:

• chr14-67588896-C-G
• chr14-67588896-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020715.3(PLEKHH1):​c.*1661C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,492 control chromosomes in the GnomAD database, including 41,661 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 0.73 (41499 hom., cov: 31)
  • Exomes 𝑓: 0.87 (162 hom.)
• Consequence: PLEKHH1 NM_020715.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526

Genes affected

PLEKHH1 (HGNC:17733): (pleckstrin homology, MyTH4 and FERM domain containing H1) Predicted to be located in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

PIGH (HGNC:8964): (phosphatidylinositol glycan anchor biosynthesis class H) This gene encodes an endoplasmic reticulum associated protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI anchor is a glycolipid found on many blood cells and which serves to anchor proteins to the cell surface. The protein encoded by this gene is a subunit of the GPI N-acetylglucosaminyl (GlcNAc) transferase that transfers GlcNAc to phosphatidylinositol (PI) on the cytoplasmic side of the endoplasmic reticulum. [provided by RefSeq, Jul 2008]

GPHN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHH1	NM_020715.3	c.*1661C>G		3_prime_UTR_variant	29/29	ENST00000329153.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHH1	ENST00000329153.10	c.*1661C>G		3_prime_UTR_variant	29/29	1	NM_020715.3	P1

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110813 AN: 151942 Hom.: 41477 Cov.: 31

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.745

GnomAD4 exome AF: 0.873 AC: 377 AN: 432 Hom.: 162 Cov.: 0 AF XY: 0.850 AC XY: 221 AN XY: 260

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.880

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.729 AC: 110878 AN: 152060 Hom.: 41499 Cov.: 31 AF XY: 0.732 AC XY: 54412 AN XY: 74322

Gnomad4 AFR AF: 0.552

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.851

Gnomad4 NFE AF: 0.809

Gnomad4 OTH AF: 0.743

Alfa AF: 0.729 Hom.: 2429

Bravo AF: 0.715

Asia WGS AF: 0.663 AC: 2306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.1
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs4902496; hg19: chr14-68055613;