1-183940583-G-A

Position:

• chr1-183940583-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_015101.4(COLGALT2):​c.1602C>T​(p.Pro534Pro) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,613,722 control chromosomes in the GnomAD database, including 31,215 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2308 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28907 hom.)
• Consequence: COLGALT2 NM_015101.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.03064
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=-0.042 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COLGALT2	NM_015101.4	c.1602C>T	p.Pro534Pro	splice_region_variant, synonymous_variant	11/12	ENST00000361927.9	NP_055916.1
COLGALT2	NM_001303420.2	c.1602C>T	p.Pro534Pro	splice_region_variant, synonymous_variant	11/12		NP_001290349.1
COLGALT2	NM_001303421.2	c.1242C>T	p.Pro414Pro	splice_region_variant, synonymous_variant	11/12		NP_001290350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COLGALT2	ENST00000361927.9	c.1602C>T	p.Pro534Pro	splice_region_variant, synonymous_variant	11/12	1	NM_015101.4	ENSP00000354960.4
COLGALT2	ENST00000649786.1	c.1602C>T	p.Pro534Pro	splice_region_variant, synonymous_variant	11/12			ENSP00000497601.1
COLGALT2	ENST00000367520.3	c.813C>T	p.Pro271Pro	splice_region_variant, synonymous_variant	6/7	2		ENSP00000356490.3
COLGALT2	ENST00000367521.5	c.426C>T	p.Pro142Pro	splice_region_variant, synonymous_variant	3/4	2		ENSP00000356491.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25165 AN: 152090 Hom.: 2307 Cov.: 32

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.188

GnomAD3 exomes AF: 0.202 AC: 50811 AN: 251430 Hom.: 5643 AF XY: 0.202 AC XY: 27459 AN XY: 135896

Gnomad AFR exome AF: 0.0869

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.207

Gnomad SAS exome AF: 0.232

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.204

GnomAD4 exome AF: 0.194 AC: 284194 AN: 1461514 Hom.: 28907 Cov.: 33 AF XY: 0.195 AC XY: 142143 AN XY: 727096

Gnomad4 AFR exome AF: 0.0850

Gnomad4 AMR exome AF: 0.298

Gnomad4 ASJ exome AF: 0.202

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.165 AC: 25181 AN: 152208 Hom.: 2308 Cov.: 32 AF XY: 0.167 AC XY: 12402 AN XY: 74420

Gnomad4 AFR AF: 0.0918

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.187

Alfa AF: 0.191 Hom.: 5796

Bravo AF: 0.172

Asia WGS AF: 0.209 AC: 724 AN: 3478

EpiCase AF: 0.196

EpiControl AF: 0.201

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	4.8
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.031
dbscSNV1_RF	Benign	0.24
SpliceAI score (max)		0.040		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: rs2296713; hg19: chr1-183909717; COSMIC: COSV62299337;