rs11046430

Positions:

• chr12-22413495-C-T

Variant summary

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

The ENST00000661495.1(C2CD5-AS1):​n.171+4088C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0978 in 151,910 control chromosomes in the GnomAD database, including 791 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 0.098 (791 hom., cov: 32)
• Consequence: C2CD5-AS1 ENST00000661495.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744

Genes affected

C2CD5-AS1 (HGNC:55961): (C2CD5 antisense RNA 1)

ST8SIA1 (HGNC:10869): (ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1) Gangliosides are membrane-bound glycosphingolipids containing sialic acid. Ganglioside GD3 is known to be important for cell adhesion and growth of cultured malignant cells. The protein encoded by this gene is a type II membrane protein that catalyzes the transfer of sialic acid from CMP-sialic acid to GM3 to produce gangliosides GD3 and GT3. The encoded protein may be found in the Golgi apparatus and is a member of glycosyltransferase family 29. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2CD5-AS1	ENST00000661495.1	n.171+4088C>T		intron_variant, non_coding_transcript_variant
C2CD5-AS1	ENST00000508615.3	n.152+4088C>T		intron_variant, non_coding_transcript_variant		5
ST8SIA1	ENST00000536558.5	n.166+23381G>A		intron_variant, non_coding_transcript_variant		3
C2CD5-AS1	ENST00000689593.1	n.135+4088C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0978 AC: 14841 AN: 151792 Hom.: 789 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0610

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.0824

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

GnomAD4 genome AF: 0.0978 AC: 14857 AN: 151910 Hom.: 791 Cov.: 32 AF XY: 0.0968 AC XY: 7190 AN XY: 74256

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0646

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.0364

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0610

Gnomad4 NFE AF: 0.0921

Gnomad4 OTH AF: 0.0867

Alfa AF: 0.101 Hom.: 106

Bravo AF: 0.0980

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.45
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11046430; hg19: chr12-22566429;