rs11562721

Positions:

• chr8-118069754-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000127.3(EXT1):​c.962+40331A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 152,084 control chromosomes in the GnomAD database, including 925 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 0.097 (925 hom., cov: 32)
• Consequence: EXT1 NM_000127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXT1	NM_000127.3	c.962+40331A>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.962+40331A>G		intron_variant		1	NM_000127.3	ENSP00000367446	P1
EXT1	ENST00000436216.2	c.330+40331A>G		intron_variant, NMD_transcript_variant		3		ENSP00000400372
EXT1	ENST00000437196.1	c.73+41220A>G		intron_variant, NMD_transcript_variant		5		ENSP00000407299

Frequencies

GnomAD3 genomes AF: 0.0970 AC: 14744 AN: 151966 Hom.: 923 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0672

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0855

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.0615

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.0971 AC: 14766 AN: 152084 Hom.: 925 Cov.: 32 AF XY: 0.0976 AC XY: 7256 AN XY: 74352

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0670

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.0226

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0855

Gnomad4 NFE AF: 0.0615

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0724 Hom.: 666

Bravo AF: 0.0960

Asia WGS AF: 0.0690 AC: 242 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.50
DANN	Benign	0.25

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: rs11562721; hg19: chr8-119081993;