rs4486225

Variant names:

• chr8-19455893-A-G
• rs4486225
• NM_001354483.2:c.851+2533T>C

Variant summary

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

The NM_001354483.2(CSGALNACT1):​c.851+2533T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,028 control chromosomes in the GnomAD database, including 22,011 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 0.53 (22011 hom., cov: 32)
• Consequence: CSGALNACT1 NM_001354483.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 7 publications found

Genes affected

CSGALNACT1 (HGNC:24290): (chondroitin sulfate N-acetylgalactosaminyltransferase 1) This gene encodes an enzyme that transfers N-acetylglucosamine (GalNAc) to the core tetrasaccharide linker and to elongating chondroitin sulfate chains in proteoglycans. Knockout of the orthologous mouse gene indicates that the protein is necessary for normal cartilage development and aggrecan metabolism. Mutations in this gene are associated with multiple sclerosis progression, and with mild skeletal dysplasia and joint laxity. [provided by RefSeq, Aug 2017]

CSGALNACT1 Gene-Disease associations (from GenCC):

• skeletal dysplasia, mild, with joint laxity and advanced bone age

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSGALNACT1	NM_001354483.2	c.851+2533T>C		intron_variant	Intron 4 of 8	ENST00000692225.2	NP_001341412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSGALNACT1	ENST00000692225.2	c.851+2533T>C		intron_variant	Intron 4 of 8		NM_001354483.2	ENSP00000509853.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81018 AN: 151910 Hom.: 21970 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.534 AC: 81121 AN: 152028 Hom.: 22011 Cov.: 32 AF XY: 0.537 AC XY: 39896 AN XY: 74290

African (AFR) AF: 0.480 AC: 19884 AN: 41440

American (AMR) AF: 0.625 AC: 9547 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1710 AN: 3472

East Asian (EAS) AF: 0.849 AC: 4384 AN: 5164

South Asian (SAS) AF: 0.574 AC: 2762 AN: 4816

European-Finnish (FIN) AF: 0.524 AC: 5535 AN: 10572

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35553 AN: 67970

Other (OTH) AF: 0.582 AC: 1229 AN: 2110

Alfa AF: 0.530 Hom.: 61388

Bravo AF: 0.542

Asia WGS AF: 0.712 AC: 2471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.33
PhyloP100		-0.19
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: rs4486225; hg19: chr8-19313404;