rs7459527

Variant names:

• chr8-117897021-A-C
• rs7459527
• NM_000127.3:c.963-59820T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-117897021-A-C
• chr8-117897021-A-T

Variant summary

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

The NM_000127.3(EXT1):​c.963-59820T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 152,188 control chromosomes in the GnomAD database, including 67,831 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 0.94 (67831 hom., cov: 31)
• Consequence: EXT1 NM_000127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.991 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXT1	NM_000127.3	MANE Select	c.963-59820T>G		intron	N/A	NP_000118.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXT1	ENST00000378204.7	TSL:1 MANE Select	c.963-59820T>G		intron	N/A	ENSP00000367446.3	Q16394
	EXT1	ENST00000436216.2	TSL:3	n.330-59820T>G		intron	N/A	ENSP00000400372.1	H7C1H6
	EXT1	ENST00000437196.1	TSL:5	n.74-61470T>G		intron	N/A	ENSP00000407299.1	F8WF54

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143148 AN: 152070 Hom.: 67777 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.945

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.986

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.957

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

GnomAD4 genome AF: 0.941 AC: 143258 AN: 152188 Hom.: 67831 Cov.: 31 AF XY: 0.942 AC XY: 70098 AN XY: 74418

African (AFR) AF: 0.830 AC: 34414 AN: 41484

American (AMR) AF: 0.945 AC: 14448 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 3378 AN: 3472

East Asian (EAS) AF: 0.899 AC: 4628 AN: 5148

South Asian (SAS) AF: 0.986 AC: 4758 AN: 4826

European-Finnish (FIN) AF: 0.993 AC: 10547 AN: 10618

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.997 AC: 67861 AN: 68036

Other (OTH) AF: 0.958 AC: 2024 AN: 2112

Alfa AF: 0.974 Hom.: 225912

Bravo AF: 0.931

Asia WGS AF: 0.923 AC: 3209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	11
DANN	Benign	0.55
PhyloP100		0.14
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: rs7459527; hg19: chr8-118909260;