rs6508461

Positions:

• chr18-26957690-G-C

Variant summary

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

The NM_031422.6(CHST9):​c.203-13324C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 151,958 control chromosomes in the GnomAD database, including 2,785 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 0.13 (2785 hom., cov: 31)
• Consequence: CHST9 NM_031422.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911

Genes affected

CHST9 (HGNC:19898): (carbohydrate sulfotransferase 9) The protein encoded by this gene belongs to the sulfotransferase 2 family. It is localized to the golgi membrane, and catalyzes the transfer of sulfate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans. Sulfate groups on carbohydrates confer highly specific functions to glycoproteins, glycolipids, and proteoglycans, and are critical for cell-cell interaction, signal transduction, and embryonic development. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Aug 2011]

AQP4-AS1 (HGNC:26399): (AQP4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST9	NM_031422.6	c.203-13324C>G		intron_variant		ENST00000618847.5	NP_113610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST9	ENST00000618847.5	c.203-13324C>G		intron_variant		1	NM_031422.6	ENSP00000480991	P1
AQP4-AS1	ENST00000578701.5	n.140+32845G>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19391 AN: 151840 Hom.: 2785 Cov.: 31

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0596

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.128 AC: 19405 AN: 151958 Hom.: 2785 Cov.: 31 AF XY: 0.125 AC XY: 9275 AN XY: 74286

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.0611

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0590

Gnomad4 FIN AF: 0.0386

Gnomad4 NFE AF: 0.0357

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0905 Hom.: 226

Bravo AF: 0.139

Asia WGS AF: 0.0320 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.41
DANN	Benign	0.40

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: rs6508461; hg19: chr18-24537654;