Genetic Variant EXT1:c.*144delA (chr8-117799567-CT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000127.3(EXT1):c.*144delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 692,404 control chromosomes in the GnomAD database, including 13,005 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.18 ( 2610 hom., cov: 26)

Exomes 𝑓: 0.34 ( 10395 hom. )

Consequence

EXT1
NM_000127.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.68

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

exostoses, multiple, type 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
chondrosarcoma
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
hereditary multiple osteochondromas
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

EXT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 8-117799567-CT-C is Benign according to our data. Variant chr8-117799567-CT-C is described in ClinVar as [Benign]. Clinvar id is 1225997.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EXT1	NM_000127.3 link	c.*144delA		3_prime_UTR_variant	Exon 11 of 11	ENST00000378204.7	NP_000118.2	Q16394

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EXT1	ENST00000378204.7 link	c.*144delA	3_prime_UTR_variant	Exon 11 of 11	1	NM_000127.3	ENSP00000367446.3	Q16394
EXT1	ENST00000684189.1 link	n.1852delA	non_coding_transcript_exon_variant	Exon 11 of 11
EXT1	ENST00000684443.1 link	n.*19delA	downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

25716

AN:

145850

Hom.:

2610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0566

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.0660

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.299

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.229

GnomAD4 exome

AF:

0.343

AC:

187390

AN:

546500

Hom.:

10395

Cov.:

AF XY:

0.346

AC XY:

97566

AN XY:

281954

show subpopulations

African (AFR)

AF:

0.224

AC:

2579

AN:

11502

American (AMR)

AF:

0.402

AC:

8036

AN:

20012

Ashkenazi Jewish (ASJ)

AF:

0.378

AC:

4853

AN:

12830

East Asian (EAS)

AF:

0.291

AC:

5615

AN:

19288

South Asian (SAS)

AF:

0.396

AC:

15095

AN:

38132

European-Finnish (FIN)

AF:

0.315

AC:

9200

AN:

29194

Middle Eastern (MID)

AF:

0.370

AC:

1005

AN:

2714

European-Non Finnish (NFE)

AF:

0.340

AC:

131752

AN:

387048

Other (OTH)

AF:

0.359

AC:

9255

AN:

25780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

6089

12178

18267

24356

30445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.176

AC:

25710

AN:

145904

Hom.:

2610

Cov.:

AF XY:

0.173

AC XY:

12262

AN XY:

70892

show subpopulations

African (AFR)

AF:

0.0566

AC:

2241

AN:

39626

American (AMR)

AF:

0.233

AC:

3415

AN:

14676

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

770

AN:

3372

East Asian (EAS)

AF:

0.0658

AC:

330

AN:

5018

South Asian (SAS)

AF:

0.195

AC:

889

AN:

4566

European-Finnish (FIN)

AF:

0.174

AC:

1605

AN:

9208

Middle Eastern (MID)

AF:

0.299

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.237

AC:

15720

AN:

66224

Other (OTH)

AF:

0.228

AC:

463

AN:

2034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

976

1952

2929

3905

4881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0583

Hom.:

Bravo

AF:

0.175

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 03, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr8-117799567-CT-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over