rs4486225

Positions:

• chr8-19455893-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CSGALNACT1	NM_001354483.2	c.851+2533T>C		intron_variant		ENST00000692225.2	NP_001341412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSGALNACT1	ENST00000692225.2	c.851+2533T>C		intron_variant			NM_001354483.2	ENSP00000509853	P1

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

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.582

Alfa AF: 0.529 Hom.: 38373

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

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: rs4486225; hg19: chr8-19313404;