8-117799567-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000127.3(EXT1):c.*144_*145insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 770,106 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (4 hom., cov: 26)
  • Exomes 𝑓: 0.013 (0 hom.)
• Consequence: EXT1 NM_000127.3 3_prime_UTR
• Clinical Significance: Likely 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-C-CT is Benign according to our data. Variant chr8-117799567-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 1190764.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00427 (625/146298) while in subpopulation AFR AF= 0.0132 (525/39684). AF 95% confidence interval is 0.0123. There are 4 homozygotes in gnomad4. There are 332 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High AC in GnomAd at 621 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EXT1	NM_000127.3	c.*144_*145insA		3_prime_UTR_variant	11/11	ENST00000378204.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EXT1	ENST00000378204.7	c.*144_*145insA		3_prime_UTR_variant	11/11	1	NM_000127.3	P1
EXT1	ENST00000684189.1	n.1852_1853insA		non_coding_transcript_exon_variant	11/11
EXT1	ENST00000684443.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.00425 AC: 621 AN: 146244 Hom.: 4 Cov.: 26

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00184

Gnomad ASJ AF: 0.00118

Gnomad EAS AF: 0.00397

Gnomad SAS AF: 0.000874

Gnomad FIN AF: 0.000214

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000542

Gnomad OTH AF: 0.00344

GnomAD4 exome AF: 0.0133 AC: 8297 AN: 623808 Hom.: 0 Cov.: 0 AF XY: 0.0131 AC XY: 4227 AN XY: 323070

Gnomad4 AFR exome AF: 0.0319

Gnomad4 AMR exome AF: 0.00954

Gnomad4 ASJ exome AF: 0.0126

Gnomad4 EAS exome AF: 0.0178

Gnomad4 SAS exome AF: 0.0101

Gnomad4 FIN exome AF: 0.0133

Gnomad4 NFE exome AF: 0.0129

Gnomad4 OTH exome AF: 0.0148

GnomAD4 genome AF: 0.00427 AC: 625 AN: 146298 Hom.: 4 Cov.: 26 AF XY: 0.00467 AC XY: 332 AN XY: 71128

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.00184

Gnomad4 ASJ AF: 0.00118

Gnomad4 EAS AF: 0.00398

Gnomad4 SAS AF: 0.000876

Gnomad4 FIN AF: 0.000214

Gnomad4 NFE AF: 0.000542

Gnomad4 OTH AF: 0.00342

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 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;