chr18-26916412-G-C

Position:

• chr18-26916412-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_031422.6(CHST9):​c.1179C>G​(p.Pro393Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,613,690 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (34 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (37 hom.)
• Consequence: CHST9 NM_031422.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.192

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:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 18-26916412-G-C is Benign according to our data. Variant chr18-26916412-G-C is described in ClinVar as [Benign]. Clinvar id is 788912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.192 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1726/152142) while in subpopulation AFR AF= 0.0398 (1654/41514). AF 95% confidence interval is 0.0382. There are 34 homozygotes in gnomad4. There are 772 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST9	NM_031422.6	c.1179C>G	p.Pro393Pro	synonymous_variant	6/6	ENST00000618847.5	NP_113610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST9	ENST00000618847.5	c.1179C>G	p.Pro393Pro	synonymous_variant	6/6	1	NM_031422.6	ENSP00000480991.1

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1717 AN: 152024 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.0397

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00272 AC: 677 AN: 249190 Hom.: 9 AF XY: 0.00205 AC XY: 277 AN XY: 135188

Gnomad AFR exome AF: 0.0403

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000620

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.00121 AC: 1763 AN: 1461548 Hom.: 37 Cov.: 31 AF XY: 0.00101 AC XY: 733 AN XY: 727092

Gnomad4 AFR exome AF: 0.0451

Gnomad4 AMR exome AF: 0.00148

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000171

Gnomad4 OTH exome AF: 0.00247

GnomAD4 genome AF: 0.0113 AC: 1726 AN: 152142 Hom.: 34 Cov.: 33 AF XY: 0.0104 AC XY: 772 AN XY: 74366

Gnomad4 AFR AF: 0.0398

Gnomad4 AMR AF: 0.00295

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00805

Alfa AF: 0.000784 Hom.: 0

Bravo AF: 0.0129

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	1.6
DANN	Benign	0.69

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: rs80190384; hg19: chr18-24496376;