19-17557161-T-C

Variant names:

• chr19-17557161-T-C
• rs3848643
• NM_024656.4:c.260+1188T>C

Variant summary

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

The NM_024656.4(COLGALT1):​c.260+1188T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 152,210 control chromosomes in the GnomAD database, including 60,364 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 0.89 (60364 hom., cov: 33)
• Consequence: COLGALT1 NM_024656.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.52
• Publications: 2 publications found

Genes affected

COLGALT1 (HGNC:26182): (collagen beta(1-O)galactosyltransferase 1) The protein encoded by this gene is one of two enzymes that transfers galactose moieties to hydroxylysine residues of collagen and mannose binding lectin. This gene is constitutively expressed and encodes a soluble protein that localizes to the endoplasmic reticulum. [provided by RefSeq, Dec 2015]

COLGALT1 Gene-Disease associations (from GenCC):

• brain small vessel disease 3

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024656.4. 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
	COLGALT1	NM_024656.4	MANE Select	c.260+1188T>C		intron	N/A	NP_078932.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLGALT1	ENST00000252599.9	TSL:1 MANE Select	c.260+1188T>C		intron	N/A	ENSP00000252599.3	Q8NBJ5
	COLGALT1	ENST00000886053.1		c.260+1188T>C		intron	N/A	ENSP00000556112.1
	COLGALT1	ENST00000886054.1		c.260+1188T>C		intron	N/A	ENSP00000556113.1

Frequencies

GnomAD3 genomes AF: 0.887 AC: 134890 AN: 152092 Hom.: 60301 Cov.: 33

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.945

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.834

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.895

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

GnomAD4 genome AF: 0.887 AC: 135015 AN: 152210 Hom.: 60364 Cov.: 33 AF XY: 0.880 AC XY: 65509 AN XY: 74416

African (AFR) AF: 0.967 AC: 40190 AN: 41558

American (AMR) AF: 0.893 AC: 13632 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.945 AC: 3282 AN: 3472

East Asian (EAS) AF: 0.563 AC: 2913 AN: 5170

South Asian (SAS) AF: 0.784 AC: 3782 AN: 4822

European-Finnish (FIN) AF: 0.834 AC: 8832 AN: 10584

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.874 AC: 59419 AN: 68016

Other (OTH) AF: 0.898 AC: 1897 AN: 2112

Alfa AF: 0.878 Hom.: 235769

Bravo AF: 0.895

Asia WGS AF: 0.719 AC: 2499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.39
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3848643; hg19: chr19-17667970;