chr8-142886016-C-T

Position:

• chr8-142886016-C-T

Variant summary

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

The ENST00000522728.5(GML):​c.182-27947C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,830 control chromosomes in the GnomAD database, including 14,197 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 0.40 (14197 hom., cov: 30)
• Consequence: GML ENST00000522728.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

GML (HGNC:4375): (glycosylphosphatidylinositol anchored molecule like) Predicted to be involved in DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; apoptotic process; and negative regulation of cell population proliferation. Predicted to be extrinsic component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GML	ENST00000522728.5	c.182-27947C>T		intron_variant		3		ENSP00000430799

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60769 AN: 151712 Hom.: 14195 Cov.: 30

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.400 AC: 60782 AN: 151830 Hom.: 14197 Cov.: 30 AF XY: 0.412 AC XY: 30552 AN XY: 74196

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.517

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.425

Alfa AF: 0.449 Hom.: 22911

Bravo AF: 0.387

Asia WGS AF: 0.585 AC: 2034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4736349; hg19: chr8-143967432;