8-117799567-CT-C

Position:

• chr8-117799567-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000127.3(EXT1):​c.*144del 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.68

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
EXT1	NM_000127.3	c.*144del		3_prime_UTR_variant	11/11	ENST00000378204.7	NP_000118.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXT1	ENST00000378204.7	c.*144del		3_prime_UTR_variant	11/11	1	NM_000127.3	ENSP00000367446	P1
EXT1	ENST00000684189.1	n.1852del		non_coding_transcript_exon_variant	11/11
EXT1	ENST00000684443.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.176 AC: 25716 AN: 145850 Hom.: 2610 Cov.: 26

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.: 0 AF XY: 0.346 AC XY: 97566 AN XY: 281954

Gnomad4 AFR exome AF: 0.224

Gnomad4 AMR exome AF: 0.402

Gnomad4 ASJ exome AF: 0.378

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.396

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.359

GnomAD4 genome AF: 0.176 AC: 25710 AN: 145904 Hom.: 2610 Cov.: 26 AF XY: 0.173 AC XY: 12262 AN XY: 70892

Gnomad4 AFR AF: 0.0566

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.0658

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.228

Bravo AF: 0.175

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 03, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs71739430; hg19: chr8-118811806;