1-184033740-A-G

Variant names:

• chr1-184033740-A-G
• rs756199
• NM_015101.4:c.263+3355T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015101.4(COLGALT2):​c.263+3355T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 151,988 control chromosomes in the GnomAD database, including 3,822 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 0.22 (3822 hom., cov: 32)
• Consequence: COLGALT2 NM_015101.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.764
• Publications: 16 publications found

Genes affected

COLGALT2 (HGNC:16790): (collagen beta(1-O)galactosyltransferase 2) Predicted to enable procollagen galactosyltransferase activity. Predicted to be involved in collagen fibril organization. Predicted to be located in endoplasmic reticulum lumen. [provided by Alliance of Genome Resources, Apr 2022]

COLGALT2 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015101.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLGALT2	NM_015101.4	MANE Select	c.263+3355T>C		intron	N/A	NP_055916.1
	COLGALT2	NM_001303420.2		c.263+3355T>C		intron	N/A	NP_001290349.1
	COLGALT2	NM_001303421.2		c.-98+3841T>C		intron	N/A	NP_001290350.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLGALT2	ENST00000361927.9	TSL:1 MANE Select	c.263+3355T>C		intron	N/A	ENSP00000354960.4
	COLGALT2	ENST00000649786.1		c.263+3355T>C		intron	N/A	ENSP00000497601.1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33288 AN: 151870 Hom.: 3824 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.219 AC: 33310 AN: 151988 Hom.: 3822 Cov.: 32 AF XY: 0.225 AC XY: 16690 AN XY: 74294

African (AFR) AF: 0.195 AC: 8068 AN: 41444

American (AMR) AF: 0.236 AC: 3605 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2414 AN: 5146

South Asian (SAS) AF: 0.280 AC: 1350 AN: 4816

European-Finnish (FIN) AF: 0.239 AC: 2523 AN: 10572

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.207 AC: 14047 AN: 67962

Other (OTH) AF: 0.217 AC: 459 AN: 2112

Alfa AF: 0.210 Hom.: 15329

Bravo AF: 0.220

Asia WGS AF: 0.352 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.82
PhyloP100		0.76
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: rs756199; hg19: chr1-184002874;