rs7459527

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXT1	NM_000127.3	c.963-59820T>G		intron_variant		ENST00000378204.7	NP_000118.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXT1	ENST00000378204.7	c.963-59820T>G		intron_variant		1	NM_000127.3	ENSP00000367446.3
EXT1	ENST00000436216.2	n.330-59820T>G		intron_variant		3		ENSP00000400372.1
EXT1	ENST00000437196.1	n.74-61470T>G		intron_variant		5		ENSP00000407299.1
EXT1	ENST00000684189.1	n.430-59820T>G		intron_variant

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

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.945

Gnomad4 ASJ AF: 0.973

Gnomad4 EAS AF: 0.899

Gnomad4 SAS AF: 0.986

Gnomad4 FIN AF: 0.993

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.958

Alfa AF: 0.986 Hom.: 134326

Bravo AF: 0.931

Asia WGS AF: 0.923 AC: 3209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	11
DANN	Benign	0.55

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: rs7459527; hg19: chr8-118909260;