rs923768

Positions:

• chr8-19673452-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354483.2(CSGALNACT1):​c.-391-71587A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,108 control chromosomes in the GnomAD database, including 16,526 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 0.46 (16526 hom., cov: 33)
• Consequence: CSGALNACT1 NM_001354483.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSGALNACT1	NM_001354483.2	c.-391-71587A>G		intron_variant		ENST00000692225.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSGALNACT1	ENST00000692225.2	c.-391-71587A>G		intron_variant			NM_001354483.2	P1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69731 AN: 151990 Hom.: 16522 Cov.: 33

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.459 AC: 69758 AN: 152108 Hom.: 16526 Cov.: 33 AF XY: 0.454 AC XY: 33783 AN XY: 74352

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.395

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.495

Alfa AF: 0.518 Hom.: 27222

Bravo AF: 0.452

Asia WGS AF: 0.488 AC: 1697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs923768; hg19: chr8-19530963;