8-19475502-A-T

Variant names:

• chr8-19475502-A-T
• rs4921648
• NM_001354483.2:c.635-16860T>A

Variant summary

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

The NM_001354483.2(CSGALNACT1):​c.635-16860T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,088 control chromosomes in the GnomAD database, including 47,411 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 0.79 (47411 hom., cov: 31)
• Consequence: CSGALNACT1 NM_001354483.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354483.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSGALNACT1	NM_001354483.2	MANE Select	c.635-16860T>A		intron	N/A	NP_001341412.1
	CSGALNACT1	NM_001130518.2		c.635-16860T>A		intron	N/A	NP_001123990.1
	CSGALNACT1	NM_001354475.2		c.635-16860T>A		intron	N/A	NP_001341404.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSGALNACT1	ENST00000692225.2	MANE Select	c.635-16860T>A		intron	N/A	ENSP00000509853.1
	CSGALNACT1	ENST00000332246.10	TSL:1	c.635-16860T>A		intron	N/A	ENSP00000330805.6
	CSGALNACT1	ENST00000454498.6	TSL:1	c.635-16860T>A		intron	N/A	ENSP00000411816.2

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119810 AN: 151970 Hom.: 47373 Cov.: 31

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.788 AC: 119902 AN: 152088 Hom.: 47411 Cov.: 31 AF XY: 0.793 AC XY: 58957 AN XY: 74340

African (AFR) AF: 0.716 AC: 29660 AN: 41450

American (AMR) AF: 0.828 AC: 12653 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2614 AN: 3472

East Asian (EAS) AF: 0.875 AC: 4521 AN: 5168

South Asian (SAS) AF: 0.792 AC: 3817 AN: 4822

European-Finnish (FIN) AF: 0.853 AC: 9028 AN: 10580

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.809 AC: 55008 AN: 68002

Other (OTH) AF: 0.812 AC: 1713 AN: 2110

Alfa AF: 0.793 Hom.: 5965

Bravo AF: 0.781

Asia WGS AF: 0.837 AC: 2908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.65
PhyloP100		0.0060
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: rs4921648; hg19: chr8-19333013;