rs11989122

Positions:

• chr8-117815600-G-A
• chr8-117815600-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EXT1	NM_000127.3	c.1633-2639C>T		intron_variant		ENST00000378204.7	NP_000118.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EXT1	ENST00000378204.7	c.1633-2639C>T		intron_variant		1	NM_000127.3	ENSP00000367446.3
EXT1	ENST00000437196.1	n.*524-2639C>T		intron_variant		5		ENSP00000407299.1
EXT1	ENST00000684189.1	n.1100-2639C>T		intron_variant

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

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.723

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.694

Alfa AF: 0.687 Hom.: 65279

Bravo AF: 0.678

Asia WGS AF: 0.577 AC: 2006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	10
DANN	Benign	0.53

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: rs11989122; hg19: chr8-118827839;