rs11989122

Variant names:

• chr8-117815600-G-A
• rs11989122
• NM_000127.3:c.1633-2639C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-117815600-G-A
• chr8-117815600-G-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.1633-2639C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,060 control chromosomes in the GnomAD database, including 34,480 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 0.67 (34480 hom., cov: 32)
• Consequence: EXT1 NM_000127.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 16 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.725 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.1633-2639C>T		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.1633-2639C>T		intron	N/A	ENSP00000367446.3	Q16394
	EXT1	ENST00000437196.1	TSL:5	n.*524-2639C>T		intron	N/A	ENSP00000407299.1	F8WF54
	EXT1	ENST00000684189.1		n.1100-2639C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102080 AN: 151942 Hom.: 34442 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.694

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.672 AC: 102176 AN: 152060 Hom.: 34480 Cov.: 32 AF XY: 0.669 AC XY: 49706 AN XY: 74334

African (AFR) AF: 0.647 AC: 26850 AN: 41474

American (AMR) AF: 0.736 AC: 11238 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2510 AN: 3472

East Asian (EAS) AF: 0.575 AC: 2972 AN: 5170

South Asian (SAS) AF: 0.605 AC: 2917 AN: 4820

European-Finnish (FIN) AF: 0.661 AC: 6993 AN: 10584

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.685 AC: 46527 AN: 67964

Other (OTH) AF: 0.694 AC: 1465 AN: 2112

Alfa AF: 0.683 Hom.: 102898

Bravo AF: 0.678

Asia WGS AF: 0.577 AC: 2006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	10
DANN	Benign	0.53
PhyloP100		0.13
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: rs11989122; hg19: chr8-118827839; COSMIC: COSV107486454;