8-117866683-A-G

Variant names:

• chr8-117866683-A-G
• rs6469713
• NM_000127.3:c.963-29482T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000127.3(EXT1):​c.963-29482T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.988 in 152,064 control chromosomes in the GnomAD database, including 74,347 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.99 (74347 hom., cov: 28)
• Consequence: EXT1 NM_000127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000127.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXT1	NM_000127.3	MANE Select	c.963-29482T>C		intron	N/A	NP_000118.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXT1	ENST00000378204.7	TSL:1 MANE Select	c.963-29482T>C		intron	N/A	ENSP00000367446.3
	EXT1	ENST00000436216.2	TSL:3	n.330-29482T>C		intron	N/A	ENSP00000400372.1
	EXT1	ENST00000437196.1	TSL:5	n.74-31132T>C		intron	N/A	ENSP00000407299.1

Frequencies

GnomAD3 genomes AF: 0.988 AC: 150176 AN: 151946 Hom.: 74287 Cov.: 28

Gnomad AFR AF: 0.997

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.983

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.989

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.989

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.988 AC: 150295 AN: 152064 Hom.: 74347 Cov.: 28 AF XY: 0.987 AC XY: 73340 AN XY: 74318

African (AFR) AF: 0.997 AC: 41357 AN: 41472

American (AMR) AF: 0.983 AC: 15011 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3453 AN: 3472

East Asian (EAS) AF: 0.847 AC: 4359 AN: 5144

South Asian (SAS) AF: 0.959 AC: 4605 AN: 4802

European-Finnish (FIN) AF: 0.989 AC: 10470 AN: 10584

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.996 AC: 67757 AN: 68008

Other (OTH) AF: 0.989 AC: 2084 AN: 2108

Alfa AF: 0.993 Hom.: 10237

Bravo AF: 0.988

Asia WGS AF: 0.908 AC: 3161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.8
DANN	Benign	0.66
PhyloP100		0.015
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6469713; hg19: chr8-118878922;