Variant 8-117812987-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000127.3(EXT1):c.1633-26C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,592,430 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 10 hom. )

Consequence

EXT1
NM_000127.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.548

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 8-117812987-G-T is Benign according to our data. Variant chr8-117812987-G-T is described in ClinVar as [Benign]. Clinvar id is 255174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00146 (223/152264) while in subpopulation EAS AF= 0.0216 (112/5176). AF 95% confidence interval is 0.0184. There are 1 homozygotes in gnomad4. There are 128 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 223 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXT1	NM_000127.3 linkuse as main transcript	c.1633-26C>A		intron_variant		ENST00000378204.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
EXT1	ENST00000378204.7 linkuse as main transcript	c.1633-26C>A	intron_variant	1	NM_000127.3	P1
EXT1	ENST00000437196.1 linkuse as main transcript	c.*524-26C>A	intron_variant, NMD_transcript_variant	5
EXT1	ENST00000684189.1 linkuse as main transcript	n.1100-26C>A	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

223

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0216

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00556

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00286

AC:

686

AN:

240176

Hom.:

AF XY:

0.00255

AC XY:

331

AN XY:

129660

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0250

Gnomad SAS exome

AF:

0.000547

Gnomad FIN exome

AF:

0.00651

Gnomad NFE exome

AF:

0.000741

Gnomad OTH exome

AF:

0.00236

GnomAD4 exome

AF:

0.00106

AC:

1523

AN:

1440166

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

753

AN XY:

717076

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.0190

Gnomad4 SAS exome

AF:

0.000718

Gnomad4 FIN exome

AF:

0.00603

Gnomad4 NFE exome

AF:

0.000260

Gnomad4 OTH exome

AF:

0.00178

GnomAD4 genome

AF:

0.00146

AC:

223

AN:

152264

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

128

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0216

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.00556

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00109

Hom.:

Bravo

AF:

0.00104

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Exostoses, multiple, type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.5

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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