chr8-142886016-C-T

Variant names:

• chr8-142886016-C-T
• rs4736349
• ENST00000522728.5:c.182-27947C>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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GML	ENST00000522728.5	c.182-27947C>T		intron_variant	Intron 3 of 4	3		ENSP00000430799.1

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;