rs11562721

Variant names:

• chr8-118069754-T-C
• rs11562721
• NM_000127.3:c.962+40331A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 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.962+40331A>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.962+40331A>G		intron	N/A	ENSP00000367446.3	Q16394
	EXT1	ENST00000436216.2	TSL:3	n.329+40331A>G		intron	N/A	ENSP00000400372.1	H7C1H6
	EXT1	ENST00000437196.1	TSL:5	n.73+41220A>G		intron	N/A	ENSP00000407299.1	F8WF54

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

African (AFR) AF: 0.171 AC: 7086 AN: 41482

American (AMR) AF: 0.0670 AC: 1024 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3468

East Asian (EAS) AF: 0.0226 AC: 117 AN: 5184

South Asian (SAS) AF: 0.138 AC: 662 AN: 4810

European-Finnish (FIN) AF: 0.0855 AC: 904 AN: 10568

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.0615 AC: 4178 AN: 67974

Other (OTH) AF: 0.108 AC: 229 AN: 2114

Alfa AF: 0.0748 Hom.: 900

Bravo AF: 0.0960

Asia WGS AF: 0.0690 AC: 242 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.50
DANN	Benign	0.25
PhyloP100		-1.2
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: rs11562721; hg19: chr8-119081993;