8-118110930-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000127.3(EXT1):c.117A>G(p.Glu39Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,613,936 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 12 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 8 hom. )

Consequence

EXT1
NM_000127.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.729

Variant links:

Genes affected

EXT1 (HGNC:3512): (exostosin glycosyltransferase 1) This gene encodes an endoplasmic reticulum-resident type II transmembrane glycosyltransferase involved in the chain elongation step of heparan sulfate biosynthesis. Mutations in this gene cause the type I form of multiple exostoses. [provided by RefSeq, Jul 2008]

EXT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 8-118110930-T-C is Benign according to our data. Variant chr8-118110930-T-C is described in ClinVar as [Benign]. Clinvar id is 255170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-118110930-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.729 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00587 (893/152226) while in subpopulation AFR AF= 0.0194 (806/41516). AF 95% confidence interval is 0.0183. There are 12 homozygotes in gnomad4. There are 423 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 893 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXT1	NM_000127.3 link	c.117A>G	p.Glu39Glu	synonymous_variant	Exon 1 of 11	ENST00000378204.7	NP_000118.2	Q16394

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EXT1	ENST00000378204.7 link	c.117A>G	p.Glu39Glu	synonymous_variant	Exon 1 of 11	1	NM_000127.3	ENSP00000367446.3		Q16394
EXT1	ENST00000437196.1 link	n.73+44A>G		intron_variant	Intron 1 of 9	5		ENSP00000407299.1		F8WF54

Frequencies

GnomAD3 genomes

AF:

0.00583

AC:

887

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00158

AC:

397

AN:

251034

Hom.:

AF XY:

0.00116

AC XY:

158

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.0190

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000150

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.000739

AC:

1080

AN:

1461710

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

459

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.0197

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000192

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00587

AC:

893

AN:

152226

Hom.:

Cov.:

AF XY:

0.00568

AC XY:

423

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0194

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.000737

Hom.:

Bravo

AF:

0.00649

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Oct 03, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Multiple congenital exostosis

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Exostoses, multiple, type 1

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.82

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over